TY - JOUR T1 - Full Characterisation of Heroin Samples Using Infrared Spectroscopy and Multivariate Calibration JF - Molecules Y1 - 2024 A1 - Eric Deconinck A1 - Lievens, Sybrien A1 - Canfyn, Michael A1 - Peter van Campenhout A1 - Loïc Debehault A1 - L. Gremeaux A1 - Margot Balcaen KW - adulterants; ATR-IR; chemometrics; diacetylmorphine; diluents; mobile detection approaches AB -

The analysis of heroin samples, before use in the protected environment of user centra, could be a supplementary service in the context of harm reduction. Infrared spectroscopy hyphenated with multivariate calibration could be a valuable asset in this context, and therefore 125 heroin samples were collected directly from users and analysed with classical chromatographic techniques. Further, MidInfrared spectra were collected for all samples, to be used in Partial Least Squares (PLS) modelling, in order to obtain qualitative and quantitative models based on real live samples. The approach showed that it was possible to identify and quantify heroin in the samples based on the collected spectral data and PLS modelling. These models were able to identify heroin correctly for 96% of the samples of the external test set with precision, specificity and sensitivity values of 100.0, 75.0 and 95.5%, respectively. For regression, a root mean squared error of prediction (RMSEP) of 0.04 was obtained, pointing at good predictive properties. Furthermore, during mass spectrometric screening, 10 different adulterants and impurities were encountered. Using the spectral data to model the presence of each of these resulted in performant models for seven of them. All models showed promising correct-classification rates (between 92 and 96%) and good values for sensitivity, specificity and precision. For codeine and morphine, the models were not satisfactory, probably due to the low concentration of these impurities as a consequence of acetylation. For methacetin, the approach failed.

VL - 29 CP - 5 M3 - 10.3390/molecules29051116 ER - TY - JOUR T1 - Spectroscopy and Chemometrics for Conformity Analysis of e-Liquids: Illegal Additive Detection and Nicotine Characterization JF - Chemosensors Y1 - 2024 A1 - Zeb Akhtar A1 - Sophia Barhdadi A1 - Kris de Braeckeleer A1 - Cedric Delporte A1 - Erwin Adams A1 - Eric Deconinck KW - e-liquids; spectroscopic techniques; chemometric techniques; data analysis AB -

Vaping electronic cigarettes (e-cigarettes) has become a popular alternative to smoking tobacco. When an e-cigarette is activated, a liquid is vaporized by heating, producing an aerosol that users inhale. While e-cigarettes are marketed as less harmful than traditional cigarettes, there are ongoing concerns about their long-term health effects, including potential lung damage. Therefore, it is essential to closely monitor and study the composition of e-liquids. E-liquids typically consist of propylene glycol, glycerin, flavorings and nicotine, though there have been reports of non-compliant nicotine concentrations and the presence of illegal additives. This study explored spectroscopic techniques to examine the conformity of nicotine labeling and detect the presence of the not-allowed additives: the caffeine, taurine, vitamin E and cannabidiol (CBD) in e-liquids. A total of 236 e-liquid samples were carefully selected for analysis. Chemometric analysis was applied to the collected data, which included mid-infrared (MIR) and near-infrared (NIR) spectra. Supervised modeling approaches such as partial least squares-discriminant analysis (PLS-DA) and soft independent modeling of class analogy (SIMCA) were employed to classify the samples, based on the presence of nicotine and the targeted additives. This study demonstrates the efficacy of MIR and NIR spectroscopic techniques in conjunction with chemometric methods (SIMCA and PLS-DA) for detecting specific molecules in e-liquids. MIR with autoscaling data preprocessing and PLS-DA achieved 100% classification rates for CBD and vitamin E, while NIR with the same approach achieved 100% for CBD and taurine. Overall, MIR combined with PLS-DA yielded the best classification across all targeted molecules, suggesting its preference as a singular technique

VL - 12 CP - 1 M3 - https://doi.org/10.3390/chemosensors12010009 ER - TY - JOUR T1 - The use of nitrous oxide whippets as a recreational drug: Hidden health risks. JF - Drug Test Anal Y1 - 2024 A1 - Bart Desmedt A1 - Eveline Verleysen A1 - Heidi Demaegdt A1 - Peter van Campenhout A1 - Erik van Miert A1 - Eric Deconinck KW - N2O; drug abuse; illegal drugs; nanoparticles; zinc oxide. AB -

Whipped cream canisters, also known as nitrous oxide whippets, are traditionally used in the culinary arts to prepare food foams. In recent years, however, these gas canisters have been cracked open and inhaled to produce a "legal" high. Users of these whippets have reported the presence of an oily residue containing metallic particles. This contamination was investigated using liquid chromatography-, gas chromatography- and inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). The particulate matter was also analyzed by scanning transmission electron microscopy (STEM) combined with energy-dispersive X-ray spectroscopy (EDX). The presence of cyclohexyl isothiocyanate was confirmed at a maximum concentration of 67 μg per whippet. ICP-MS and ICP-OES analysis revealed the presence of mainly iron and zinc, but also, traces of aluminum, chromium, cobalt, nickel, and lead were found. STEM-EDX analysis confirmed the presence of nano-sized particles containing iron and zinc. When simulating inhalation, using the multiple path particle dosimetry model, it was confirmed that these nano-sized particles can reach the deeper parts of the lungs. Most users assume that inhaling a food-grade nitrous oxide whippet for a "legal" high poses no risks. However, this research shows that users are exposed to cyclohexyl isothiocyanate, a substance classified as a respiratory sensitizer. The presence of zinc in the particulate matter could potentially be linked to lung lesions.

CP - 16 M3 - 10.1002/dta.3518 ER - TY - JOUR T1 - The analysis of cannabinoids in e-cigarette liquids using LC-HRAM-MS and LC-UV. JF - J Pharm Biomed Anal Y1 - 2023 A1 - Sophia Barhdadi A1 - Patricia Courselle A1 - Eric Deconinck A1 - Celine Vanhee KW - Cannabidiol KW - Cannabinoids KW - cannabis KW - Chromatography, Liquid KW - Dronabinol KW - Electronic Nicotine Delivery Systems KW - Mass Spectrometry AB -

The use of cannabidiol or CBD products has skyrocketed in the last five years due to the alleged therapeutic benefits, a low potential for abuse and lack of the typical psychoactive effects associated with the use of cannabis products containing high levels of ∆9-tetrahydrocannabinol (∆9-THC). In Belgium, CBD-containing e-liquids with a total THC content lower than 0.2% (w/w) are currently legal. In order to verify the compliance of the different CBD-containing e-cigarette liquids that are available to the Belgian population, a method was developed for screening of 17 cannabinoids and to quantify the major cannabinoids such as CBD, CBDA, ∆9-THC and ∆9-THCA. The latter was fully validated using the 'total error' approach, applying accuracy profiles and conforming to ISO17025. None of the analysed samples exceeded the legal limit for the total amount of ∆9-THC present. However, of the 20 CBD-liquids investigated in this study, only 30% of the samples contained an amount of CBD that was within 10% deviation of the label claim. Moreover, the CBD e-liquids labelled "full/broad spectrum" consisted of several minor alkaloids in comparison to the "classic" CBD e-liquids where the acidic forms of the cannabinoids were not present. Currently, no legislation is available for the regulation of CBD e-liquids, however these results indicate that quality controls are pertinent especially concerning the discrepancy in CBD label accuracy.

VL - 230 M3 - 10.1016/j.jpba.2023.115394 ER - TY - JOUR T1 - The analysis of cannabinoids in e-cigarette liquids using LC-HRAM-MS and LC-UV JF - Journal of Pharmaceutical and Biomedical Analysis Y1 - 2023 A1 - Sophia Barhdadi A1 - Patricia Courselle A1 - Eric Deconinck A1 - Celine Vanhee KW - Cannabinoids KW - CBD-liquids KW - e-cigarettes KW - LC-HRAM-MS AB -

The use of cannabidiol or CBD products has skyrocketed in the last five years due to the alleged therapeutic benefits, a low potential for abuse and lack of the typical psychoactive effects associated with the use of cannabis products containing high levels of ∆9-tetrahydrocannabinol (∆9-THC). In Belgium, CBD-containing e-liquids with a total THC content lower than 0.2% (w/w) are currently legal. In order to verify the compliance of the different CBD-containing e-cigarette liquids that are available to the Belgian population, a method was developed for screening of 17 cannabinoids and to quantify the major cannabinoids such as CBD, CBDA, ∆9-THC and ∆9-THCA. The latter was fully validated using the 'total error' approach, applying accuracy profiles and conforming to ISO17025. None of the analysed samples exceeded the legal limit for the total amount of ∆9-THC present. However, of the 20 CBD-liquids investigated in this study, only 30% of the samples contained an amount of CBD that was within 10% deviation of the label claim. Moreover, the CBD e-liquids labelled "full/broad spectrum" consisted of several minor alkaloids in comparison to the "classic" CBD e-liquids where the acidic forms of the cannabinoids were not present. Currently, no legislation is available for the regulation of CBD e-liquids, however these results indicate that quality controls are pertinent especially concerning the discrepancy in CBD label accuracy.

VL - 230 M3 - 10.1016/j.jpba.2023.115394 ER - TY - THES T1 - THE ANALYSIS OF ILLICIT DRUGS COLLECTED DURING A SUMMER FESTIVAL AND EVALUATION OF THE NARCOREADER FOR ON-SITE ANALYSIS OF MDMA Y1 - 2023 A1 - Marie-Arlette Pollet A1 - Eric Deconinck A1 - Michael Canfyn KW - Amphetamine KW - Cocaine KW - COVID-19 KW - GC-FID KW - GC-MS KW - identification KW - ketamine KW - MDMA KW - mid-IR KW - Narcoreader KW - near-IR KW - On-site KW - Quantification KW - RAMAN KW - UV spectroscopy AB -

Background: The most used on-site methods to identify illicit drugs consist of color tests
or spectroscopic methods with as a downside the lack of accuracy and selectivity. The law
still requires confirmation of these results with chromatographic methods. These
conventional methods are precise but time-consuming and of high cost. There is a need
for more rapid and still accurate analysis, with cost-effective and portable methods.
Aim: As the first goal of this study, a selection of drug samples is analysed and the results
are compared with statistics from Belgium and Europe for the years 2019, 2020 and 2021.
This is to portray the possible influence of COVID-19 on drugs. Secondly, the suspected
MDMA samples are analysed with four alternative techniques. The pros and cons are
compared of these alternative methods for on-site use by non-experts.
Methods: The samples are identified with GC-MS and quantified with UV-spectroscopy.
The obtained results are compared with statistics from the statistical bulletin and the
European Drug Report. The suspected MDMA samples are identified with mid-IR, near-IR,
Raman spectroscopy and the Narcoreader. The results of these four alternative devices are
compared with the conventional methods.
Results: The MDMA dosage in tablets and the MDMA purity in crystals followed an
increasing trend in Belgium. The purity of cocaine stays quite stable in Belgium. The purity
of amphetamine showed fluctuations in Belgium, with an important increase in median
purity in 2022. After weighing the pros and cons of the alternative methods, the mid-IR
device had all over the best results and could be far more attractive for on-site use in its
already existing portable format. The Narcoreader had also good results and
characteristics. It is portable, user-friendly, fast and precise.
Conclusion: The comparison of the statistics is not representative due to the lack of
statistics and sampling in different sources. It is interesting to portray how the pandemic
could influence the purities and dosages of illicit drugs, although the correlation cannot be
assured. The search for an ideal portable device for on-site identification should include
more recent and portable spectroscopic devices to make a fair match with the novel
Narcoreader.

PB - VUB CY - Brussels, Belgium ER - TY - JOUR T1 - Applicability of the DPRA on mixture testing: challenges and opportunities. JF - Arch Toxicol Y1 - 2023 A1 - Quinten Marcelis A1 - Eric Deconinck A1 - Rogiers, Vera A1 - Vanhaecke, Tamara A1 - Bart Desmedt KW - Animal Testing Alternatives KW - Animals KW - Peptides AB -

The in chemico direct peptide reactivity assay (DPRA) is validated to assess protein reactivity of chemical compounds, relating to the molecular initiating event of skin sensitization induction. According to OECD TG 442C, the DPRA is technically applicable to test multi-constituent substances and mixtures of known composition, even though limited experimental data are publicly available. First, we assessed the DPRA's predictive capability for individual substances, but at concentrations other than the recommended 100 mM, i.e., based on the LLNA EC3 concentration (Experiment A). Next, the applicability of the DPRA to test unknown mixtures was assessed (Experiment B). Here, the complexity of unknown mixtures was reduced to mixtures containing either two known skin sensitizers with varying potencies, or a combination of a skin sensitizer with a non-skin sensitizer, or multiple non-sensitizers. Experiments A and B revealed that one extremely potent sensitizer (oxazolone) was incorrectly classified as a non-sensitizer when tested at its low EC3 concentration of 0.4 mM instead of the suggested molar excess conditions of 100 mM (Experiments A). For binary mixtures tested in experiments B, the DPRA was able to distinguish all skin sensitizers and the strongest skin sensitizer in the mixture was determinant for the overall peptide depletion of a sensitizer. In conclusion, we confirmed that the DPRA test method can be used efficiently for well-known characterized mixtures. However, when deviating from the recommended testing concentration of 100 mM, caution should be taken in case of negative results, limiting the DPRA's applicability for mixtures of unknown composition.

VL - 97 CP - 9 M3 - 10.1007/s00204-023-03551-y ER - TY - JOUR T1 - Challenges in Drug Surveillance: Strengthening the Analysis of New Psychoactive Substances by Harmonizing Drug Checking Services in Proficiency Testing. JF - Int J Environ Res Public Health Y1 - 2023 A1 - Margot Balcaen A1 - Mireia Ventura A1 - Cristina Gil A1 - Anton Luf A1 - Daniel Martins A1 - Mar Cunha A1 - Karsten Tögel-Lins A1 - Danny Wolf A1 - Peter Blanckaert A1 - Eric Deconinck KW - Chromatography, Liquid KW - Gas Chromatography-Mass Spectrometry KW - harm reduction KW - Humans KW - psychotropic drugs AB -

BACKGROUND: Drug checking is a proven harm reduction strategy and provides real-time information on the market of new psychoactive substances (NPS). It combines chemical analysis of samples with direct engagement with people who use drugs (PWUD), giving the ability to increase preparedness and responsiveness towards NPS. Next to that, it supports rapid identification of potential unwitting consumption. However, NPS cause a toxicological battle for the researchers, as factors such as the unpredictability and quick shift of the market complicate the detection.

METHODS: To evaluate challenges posed towards drug checking services, proficiency testing was set up to evaluate existing analytical techniques and investigate the capability to correctly identify circulating NPS. Twenty blind substances, covering the most common categories of substances, were analyzed according to the existing protocols of the existing drug checking services, including several analytical methods such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with diode array detector (LC-DAD).

RESULTS: The proficiency test scores range from 80 to 97.5% accuracy. The most common issues and errors are mainly unidentified compounds, presumably due to no up-to-date libraries, and/ or confusion between structural isomers, such as 3- and 4-chloroethcathinone, or structural analogs, such as MIPLA (N-methyl-N-isopropyl lysergamide) and LSD (D-lysergic acid diethylamide).

CONCLUSIONS: The participating drug checking services have access to adequate analytical tools to provide feedback to drug users and provide up-to-date information on NPS.

VL - 20 CP - 5 M3 - 10.3390/ijerph20054628 ER - TY - JOUR T1 - Clustering of Tadalafil API Samples According to their Manufacturer in the Context of API Falsification Detection JF - Journal of Pharmaceutical Sciences Y1 - 2023 A1 - Eric Deconinck A1 - M. Raimondo A1 - A. Borioni A1 - Y. Grange A1 - H. Rebière A1 - A. Mihailova A1 - O. Bøyum A1 - J.K. Maurin A1 - K. Pioruńska-Sędłak A1 - Olsen, L. Stengelshøj A1 - J. Acevska A1 - K. Brezovska A1 - T. Rundlöf A1 - M.J. Portela A1 - S. Meieranz A1 - M. Miquel A1 - M. Bertrand KW - APIs KW - fingerprint KW - GEON/OMCL network KW - illegal medicinal products KW - Tadalafil AB -

This paper reports the results of the active pharmaceutical ingredient (API) fingerprint study, organised by the General European Official Medicines Control Laboratory Network (GEON), on tadalafil. A classical market surveillance study, evaluating compliance to the European Pharmacopoeia, was combined with a fingerprint study, the latter to obtain characteristic data for the different manufacturers, allowing the network laboratories to conduct authenticity tests for future samples, as well as to detect substandard and falsified samples.

In total, 46 tadalafil API samples from 13 different manufacturers were collected. For all samples fingerprint data was collected through analysis of impurities and residual solvents, mass spectrometric screening, X-ray powder diffraction and proton nuclear magnetic resonance (1H-NMR). Chemometric analysis revealed that all manufacturers could be characterised based on the impurity, residual solvent and 1H-NMR data. Future suspicious samples in the network will therefore be analysed with these techniques in order to attribute the sample to one of the manufacturers. If the sample cannot be attributed, a more profound investigation will be necessary to reveal the origin of the sample. In cases where the suspect sample is claimed to be from one of the manufacturers included in this study, analysis can be limited to the test distinguishing that manufacturer.

VL - 112 CP - 11 M3 - 10.1016/j.xphs.2023.05.015 ER - TY - Generic T1 - COMBINATION OF CHEMOMETRICS AND MULTIDIMENSIONAL FINGERPRINTING FOR DETECTION OF REGULATED PLANTS IN PLANT FOOD SUPPLEMENTS Y1 - 2023 A1 - Surbhi Ranjan A1 - Erwin Adams A1 - Eric Deconinck KW - Chromatographic fingerprints KW - Herbal food supplments AB -

Plant food supplements have shown a rising trend in their consumption in the western world. The extensive marketing campaigns and availability through various different platforms can be rendered as catalysts for their popularity. In regards to the Belgian market, suspicious samples entering the border generate serious concerns, necessitating an efficient screening approach for detection of the regulated plants in plant food supplements.

 

This study aims at developing a chemometric approach coupled with fingerprinting for detection of four regulated plants which are commonly used in plant food supplements with slimming potential: Aristolochia fanghi, Ilex paraguariensis, Garcinia cambogia and Hoodia gordonii. A chromatographic method was developed using ultra-high performance liquid chromatography with diode array detector (DAD). Furthermore, selection of orthogonal wavelengths was made to extract maximum information from the fingerprints by performing a correlation analysis on the DAD data. Chemometric analysis was carried out using two approaches: 1. binary models for each plant separately and 2. multiclass models. The data were corrected for time shifts using correlation optimized warping and further pretreated using classical techniques like signal noise variate, autoscaling and derivatives), before being subjected to partial least square – discriminate analysis. A minimum of 86% correct classification rate for external test set validation (17 sample for binary dataset and 59 samples for multiclass dataset) was observed for all the plants.

 

Analysis for twelve plant food supplements having slimming as indication, seized by the Belgian Federal Agency for Medicines and Health Products, was carried out in order to classify the plants using the developed models. Out of the 12 samples, 10 were found to be positive for the regulated plants with the binary models, whereas 11 were found positive when classified using the multiclass model. Even though both models showed good correct classification rates (%), the multiclass model could give problems when two or more of the targeted plants are present, since it is only able to classify with one plant in contrast to using different binary models. Therefore, binary models might be preferred over multiclass models. Furthermore, it can also be concluded that a combination of chemometrics and fingerprinting shows positive feasibility for classifying plants using their characteristic fingerprint profiles.

JF - 21st Forum of Pharmaceutical Sciences PB - BGFW CY - Blanckenberghe, Belgium CP - BGFW ER - TY - JOUR T1 - The Development and Validation of a Targeted LC-HRAM-MS/MS Methodology to Separate and Quantify p-Synephrine and m-Synephrine in Dietary Supplements and Herbal Preparations JF - Separations Y1 - 2023 A1 - Celine Vanhee A1 - Sophia Barhdadi A1 - Angélique Kamugisha A1 - Tanika Van Mulders A1 - Kevin Vanbrusselen A1 - Marie Willocx A1 - Eric Deconinck VL - 10 CP - 8 M3 - 10.3390/separations10080444 ER - TY - JOUR T1 - Evaluation of an electrochemical sensor and comparison with spectroscopic approaches as used today in practice for harm reduction in a festival setting-A case study: Analysis of 3,4-methylenedioxymethamphetamine samples JF - Drug Test Anal Y1 - 2023 A1 - Eric Deconinck A1 - Marie Polet A1 - Michael Canfyn A1 - Céline Duchateau A1 - Kris De Braekeleer A1 - Robin Van Echelpoel A1 - Karolien De Wael A1 - L. Gremeaux A1 - Maarten Degreef A1 - Margot Balcaen KW - ATR-(N)IR KW - drug checking KW - electrochemical detection KW - MDMA KW - Mobile detection approaches AB -

More and more countries and organisations emphasise the value of harm reduction measures in the context of illicit drug use and abuse. One of these measures is drug checking, a preventive action that can represent a quick win by tailored consultation on the risks of substance use upon analytical screening of a submitted sample. Unlike drop-in centres that operate within a fixed setting, enabling drug checking in a harm reduction context at events requires portable, easy to use analytical approaches, operated by personnel with limited knowledge of analytical chemistry. In this case study, four different approaches were compared for the characterisation of 3,4-methylenedioxymethamphetamine samples and this in the way the approaches would be applied today in an event context. The four approaches are mid-infrared (MIR), near-infrared, and Raman spectroscopy, which are today used in drug checking context in Belgium, as well as an electrochemical sensor approach initially developed in the context of law enforcement at ports. The MIR and the electrochemical approach came out best, with the latter allowing for a direct straightforward analysis of the percentage 3,4-methylenedioxymethamphetamine (as base equivalent) in the samples. However, MIR has the advantage that, in a broader drug checking context, it allows to screen for several molecules and so is able to identify unexpected active components or at least the group to which such components belong. The latter is also an important advantage in the context of the growing emergence of new psychotropic substances.

M3 - 10.1002/dta.3625 ER - TY - BOOK T1 - HPLC for Analysis of Substandard and Falsified Medicinal Products T2 - HPLC for Analysis of Substandard and Falsified Medicinal Products Y1 - 2023 A1 - Eric Deconinck A1 - Celine Vanhee KW - Counterfeit medicines KW - HPLC AB -

NA

JF - HPLC for Analysis of Substandard and Falsified Medicinal Products PB - Elsevier CY - Amsterdam, the Netherlands CP - 2 M3 - 10.1201/9781003270461-2 ER - TY - Generic T1 - MSSIP007 on Nootropics Y1 - 2023 A1 - Eric Deconinck A1 - Celine Vanhee KW - Illegal medicines KW - nootropics AB -

Reporting on the status of the 7th MSSIP study of the FM WG of EDQM

JF - 23th meeting of the Falsified Medicines Working Group EDQM PB - EDQM CY - Madrid, Spain ER - TY - JOUR T1 - Multidimensional Chromatographic Fingerprinting Combined with Chemometrics for the Identification of Regulated Plants in Suspicious Plant Food Supplements. JF - Molecules Y1 - 2023 A1 - Surbhi Ranjan A1 - Erwin Adams A1 - Eric Deconinck KW - Chemometrics KW - Chromatography, High Pressure Liquid KW - Dietary Supplements KW - Discriminant Analysis KW - Least-Squares Analysis KW - Plants AB -

The popularity of plant food supplements has seen explosive growth all over the world, making them susceptible to adulteration and fraud. This necessitates a screening approach for the detection of regulated plants in plant food supplements, which are usually composed of complex plant mixtures, thus making the approach not so straightforward. This paper aims to tackle this problem by developing a multidimensional chromatographic fingerprinting method aided by chemometrics. To render more specificity to the chromatogram, a multidimensional fingerprint (absorbance × wavelength × retention time) was considered. This was achieved by selecting several wavelengths through a correlation analysis. The data were recorded using ultra-high-performance liquid chromatography (UHPLC) coupled with diode array detection (DAD). Chemometric modelling was performed by partial least squares-discriminant analysis (PLS-DA) through (a) binary modelling and (b) multiclass modelling. The correct classification rates (ccr%) by cross-validation, modelling, and external test set validation were satisfactory for both approaches, but upon further comparison, binary models were preferred. As a proof of concept, the models were applied to twelve samples for the detection of four regulated plants. Overall, it was revealed that the combination of multidimensional fingerprinting data with chemometrics was feasible for the identification of regulated plants in complex botanical matrices.

VL - 28 CP - 8 M3 - 10.3390/molecules28083632 ER - TY - Generic T1 - Multidimensional chromatographic fingerprinting combined with chemometrics for the identification of regulated plants in suspicious plant food supplements Y1 - 2023 A1 - Surbhi Ranjan A1 - Adam, E A1 - Eric Deconinck KW - fingerprinting KW - plant food supplements AB -

An undeniable increase in consumption and sales of plant food supplements (PFS), especially in the western world, is observed. High consumer demands increased the vulnerability of these products to malpractices such as adulteration and fraud, which further led to opening up various illicit channels for their purchase. Therefore, some of these products may be ‘suspicious’ and a risk for consumers health.

 

This study aims at developing a screening approach for detection of four regulated plants commonly encountered in PFS claiming weight-loss as indication. However, PFS usually are composed of mixtures of different plants resulting into a not so straightforward approach for their detection. In order to tackle this problem, a feasibility study based on a combination of chemometrics and multidimensional fingerprints recorded using chromatography was carried out.

 

Chromatographic fingerprints were developed using ultra-high performance liquid chromatography with diode array detection. The obtained multidimensional fingerprint data for a herbal reference standard (absorbance × wavelengths × time points) were used for selection of orthogonal wavelengths by conducting a correlation analysis. After preparation of triturations, recording of the fingerprints and creation of datasets (corrected for shifts in retention times using correlation optimized warping),  partial least squares – discriminant analysis was applied to construct classification models. Two approaches for modelling were explored: (a) binary modelling and (b) multiclass modelling. The correct classification rate % (ccr%) for cross validation, modelling and external test prediction were used to select the optimal model for each plant. For both binary modelling and multiclass modelling, a ccr% above 85% for external test set validation was observed for all the plants.

 

As a proof of concept, 12 weight-loss PFS, seized by the Belgian Federal Agency for Medicines and Health Products, were classified using the above developed models. 10 out of 12 samples were suggestively found to be positive by binary modelling whereas 11 were found positive with multiclass modelling. Despite both models having good ccr%, multiclass modelling was unable to detect multiple plants in samples. Therefore, a preference of binary models over multiclass models could be made. Furthermore, it can be concluded that the combination of chemometrics and multi-wavelength chromatographic fingerprinting is a promising approach for identifying plants using in herbal mixtures.

JF - Recent Developments In Pharmaceutical Analysis (RDPA 2023) PB - Italian Chemical Society CY - Novara, Italy CP - Italian Chemical Society ER - TY - Generic T1 - Reorientation of scope of OMCL API Working Group - Change of focus of future MSS and MSSFP studies Y1 - 2023 A1 - Eric Deconinck A1 - Jelena Acevska KW - API-testing KW - Chemometrics KW - fingerprint studies AB -

NA

JF - AdGEON meeting December 2023 PB - EDQM CY - Online CP - EDQM ER - TY - JOUR T1 - Response to letter to the editor: “Comments on ‘discrepancies between validated GC‐FID and UHPLC‐DAD methods for the analysis of Δ‐9‐THC and CBD in dried hemp flowers’” JF - Drug Testing and Analysis Y1 - 2023 A1 - Eric Deconinck A1 - Michaël Canfyn A1 - Céline Duchateau A1 - De Braekeleer, Kris KW - CBD KW - delta-9-THC KW - dried hemp flowers VL - 15 CP - 2 M3 - 10.1002/dta.3388 ER - TY - THES T1 - RETAIL DRUG QUALITY PROJECT ON HEROIN: A QUALITATIVE AND QUANTITATIVE APPROACH Y1 - 2023 A1 - Sybrien Lievens A1 - Eric Deconinck A1 - Michael Canfyn A1 - Margot Balcaen KW - adulterants KW - Heroine KW - Narcoreader AB -

thesis

PB - VUB CY - Brussels, Belgium ER - TY - Generic T1 - Spectroscopic approaches for conformity analysis of e-liquids Y1 - 2023 A1 - Zeb Akhtar A1 - Sophia Barhdadi A1 - Erwin Adams A1 - Eric Deconinck KW - e-liquids KW - IR spectroscopy AB -

E-liquids are liquids used in e-cigarettes. They are responsible for creating the vapor that is inhaled by the user. E-cigarettes were created with the intention of assisting smokers in quitting because they are believed to be less dangerous than conventional combustible cigarettes. With a range of flavors and nicotine levels to choose from, as well as the presentation as “the healthier option” and cost-effectiveness, it's no wonder that e-liquids have become increasingly popular in the last 20 years, particularly with younger people. Though, vaping is not without health concerns. The long-term effects  are still not fully understood, and there have been reports of health problems associated with e-cigarette use, including lung damage. Therefore, it is necessary to monitor the compositions of the products on the market and conduct surveillance studies. In Belgium this is performed under the coordination of the Federal Public Service of public health.

E-liquids typically contain four main ingredients: propylene glycol, glycerin, flavorings and nicotine. The latter is of course not present in zero liquids. The primary issue is the content of nicotine. Previous reports showed that nicotine concentrations are not compliant to the label claim, with mean deviations between 5% and 20%. Also zero liquids containing nicotine were encountered. Another issue is the presence of  additives, illegal according to the European Directive. Some of the most important are caffeine, taurine and vitamin E. Cannabidiol (CBD), which is in the gray zone of the legislation, was also taken into account of this study, due to its popularity.

In this study spectroscopic approaches were explored to check the label conformity for nicotine and the presence of caffeine, taurine, vitamin E and CBD in e-liquids. Therefore a set of 236 e-liquids was selected. Since samples with caffeine, taurine, CBD and vitamin E as additives were hard to find, some of the samples were split in two and one of both aliquots was spiked with the targeted additives in realistic concentrations. After sample set preparation, mid-infrared, near-infrared and Raman spectra were recorded for all samples. After obtaining the data matrices, chemometric analysis was performed. For each type of data, the sample matrix was split into a training and  test set. Spectroscopic data were preprocessed before modelling. Next to baseline correction, classical preprocessing techniques like standard normal variate (SNV), derivatives and scaling were explored. In a first step, supervised modelling, using partial least squares-discriminant analysis (PLS-DA) and soft independent modelling by class analogy (SIMCA), was used to classify samples according to the presence of nicotine and/or the targeted additives. The results allowed to classify samples according to nicotine and present additives. So, their presence in new suspected samples could be detected. In a second step, PLS regression was applied to estimate the nicotine concentration and check the label conformity.

JF - 21st Forum of Pharmaceutical Sciences PB - BGFW CY - Blanckenberghe, Belgium CP - BGFW ER - TY - JOUR T1 - Substandard and falsified ivermectin tablets obtained for self-medication during the COVID-19 pandemic as a source of potential harm. JF - Drug Test Anal Y1 - 2023 A1 - Celine Vanhee A1 - Bram Jacobs A1 - Angélique Kamugisha A1 - Michael Canfyn A1 - Hans Van Der Meersch A1 - Bart Ceyssens A1 - Eric Deconinck A1 - Koenraad Van Hoorde A1 - Marie Willocx AB -

In 2019, a global viral pandemic, due to the SARS-CoV-2 virus, broke out. Soon after, the search for a vaccine and/or antiviral medicine began. One of the candidate antiviral medicines tested was ivermectin. Although several health authorities warned the public against the use of this medicine outside clinical trials, the drug was widely used at the end of 2020 and in 2021. Simultaneously, several reports started to emerge demonstrating serious adverse effects after self-medicating with ivermectin. It stands to reason that the self-administration of substandard or falsified (SF) medicines bearing harmful quality deficiencies have contributed to this phenomenon. In order to have a better view on the nature of these harmful quality deficiencies, SF ivermectin samples, intercepted in large quantities by the Belgian regulatory agencies during the period 2021-2022, were analyzed in our official medicines control laboratory. None of the samples (n = 19) were compliant to the quality criteria applicable to medicinal products. These SF products either suffered from a systematic underdosing of the active pharmaceutical ingredient or were severely contaminated with bacteria, two of which were contaminated with known pathogens that cause gastrointestinal illness upon oral intake. In addition to the direct risks of self-medicating with such a product, the improper usage and dosage of ivermectin medication might also facilitate ivermectin tolerance or resistance in parasites. This may have detrimental consequences on a global scale, certainly as the number of newly developed active pharmaceutical ingredients that can safely be used to combat parasites is rather scarce.

M3 - 10.1002/dta.3618 ER - TY - JOUR T1 - Substandard and falsified ivermectin tablets obtained for self‐medication during the COVID‐19 pandemic as a source of potential harmAbstract JF - Drug Testing and Analysis Y1 - 2023 A1 - Celine Vanhee A1 - Bram Jacobs A1 - Angélique Kamugisha A1 - Michael Canfyn A1 - Hans Van Der Meersch A1 - Bart Ceyssens A1 - Eric Deconinck A1 - Koenraad Van Hoorde A1 - Marie Willocx M3 - 10.1002/dta.3618 ER - TY - JOUR T1 - Uncovering the Quality Deficiencies with Potentially Harmful Effects in Substandard and Falsified PDE-5 Inhibitors Seized by Belgian Controlling Agencies JF - Forensic Sciences Y1 - 2023 A1 - Celine Vanhee A1 - Bram Jacobs A1 - Marcella Mori A1 - Angelique Kamugisha A1 - Loïc Debehault A1 - Michael Canfyn A1 - Bart Ceyssens A1 - Hans Van Der Meersch A1 - Koenraad Van Hoorde A1 - Eric Deconinck A1 - Marie Willocx VL - 3 CP - 3 M3 - 10.3390/forensicsci3030031 ER - TY - JOUR T1 - Uncovering the Quality Deficiencies with Potentially Harmful Effects in Substandard and Falsified PDE-5 Inhibitors Seized by Belgian Controlling Agencies JF - Forensic Sciences Y1 - 2023 A1 - Celine Vanhee A1 - Bram Jacobs A1 - Marcella Mori A1 - Angélique Kamugisha A1 - Loïc Debehault A1 - Michael Canfyn A1 - Bart Ceyssens A1 - Hans Van Der Meersch A1 - Koenraad Van Hoorde A1 - Eric Deconinck A1 - Marie Willocx KW - Mass Spectrometry KW - microbiology KW - PDE-5 inhibitors KW - substandard drugs AB -

: Illicit PDE-5 inhibitors are frequently encountered by regulatory agencies. Self-medicating with substandard and falsified (SF) PDE-5 inhibitors could be dangerous as they are likely taken without any medical supervision and might be of poor quality which could result in adverse reactions. In order to provide an overview of the quality deficiencies present in recently seized illicit PDE-5 samples that may pose health risks, we set out to identify the products’ different chemical and/or biological risks. Our results indicate that 38% of the samples harbored a chemical risk including the significant exceedance of the maximum recommended dosage, a large heterogeneity in API content between the different tablets in the same package or blister and the presence of only 40% of the claimed dosage. Moreover, our results also demonstrate that 16 of the 32 samples were not compliant with the internationally set microbiological quality standards. Startlingly, two samples were severely contaminated with potentially pathogenic bacteria, which could result in a gastrointestinal illness upon oral intake.

VL - 3 CP - 3 M3 - 10.3390/forensicsci3030031 ER - TY - JOUR T1 - Uncovering the Quality Deficiencies with Potentially Harmful Effects in Substandard and Falsified PDE-5 Inhibitors Seized by Belgian Controlling Agencies JF - Forensic Sciences Y1 - 2023 A1 - Celine Vanhee A1 - Bram Jacobs A1 - Marcella Mori A1 - Angélique Kamugisha A1 - Loïc Debehault A1 - Michael Canfyn A1 - Bart Ceyssens A1 - Hans Van Der Meersch A1 - Koenraad Van Hoorde A1 - Eric Deconinck A1 - Marie Willocx VL - 3 CP - 3 M3 - 10.3390/forensicsci3030031 ER - TY - Generic T1 - The analysis of cannabinoids in e-cigarettes liquids using LC-HR-MS and LC-UV Y1 - 2022 A1 - Sophia Barhdadi A1 - Patricia Courselle A1 - Eric Deconinck A1 - Celine Vanhee JF - 17th International Symposium on Hyphenated Techniques in Chromatography and Separation Technology (HTC-17) PB - Royal Flemish Chemical Society (KVCV) and the Separation Science Group of the Royal Society of Chemistry (SSG RSC). CY - Ghent, Belgium CP - Royal Flemish Chemical Society (KVCV) and the Separation Science Group of the Royal Society of Chemistry (SSG RSC). ER - TY - Generic T1 - Benefits of Chemometrics for OMCLs Y1 - 2022 A1 - Jelena Acevska A1 - Eric Deconinck A1 - Hervé Ribière A1 - Mariangela Raimondo JF - Combating Counterfeit and Other Illegal Medicines: 4th Symposium for OMCLs: New trends, new frontiers CP - EDQM ER - TY - JOUR T1 - Chemometrics and infrared spectroscopy – A winning team for the analysis of illicit drug productsAbstract JF - Reviews in Analytical Chemistry Y1 - 2022 A1 - Eric Deconinck A1 - Céline Duchateau A1 - Margot Balcaen A1 - L. Gremeaux A1 - Patricia Courselle KW - Chemometrics KW - illicit drugs KW - infrared spectroscopy KW - Raman spectroscopy AB -

Spectroscopic techniques such as infrared spectroscopy
and Raman spectroscopy are used for a long
time in the context of the analysis of illicit drugs, and
their use is increasing due to the development of more
performant portable devices and easy application in the
context of harm reduction through drug checking or
onsite forensic analysis. Although these instruments are
routinely used with a spectral library, the importance of
chemometric techniques to extract relevant information
and give a full characterisation of samples, especially in
the context of adulteration, is increasing. This review
gives an overview of the applications described in the
context of the analysis of illicit drug products exploiting
the advantages of the combination of spectroscopy with
chemometrics. Next to an overview of the literature, the
review also tries to emphasize the shortcomings of the
presented research papers and to give an incentive to
what is needed to include chemometrics as a part of the
daily routine of drug checking services and mobile forensic
applications.

VL - 41 CP - 1 M3 - 10.1515/revac-2022-0046 ER - TY - THES T1 - CHROMATOGRAPHIC FINGERPRINT DEVELOPMENT FOR THE DETECTION OF TRIBULUS TERRESTRIS IN PLANT FOOD SUPPLEMENTS Y1 - 2022 A1 - Sano-Magnifique Dusingizimana A1 - Surbhi Ranjan A1 - Eric Deconinck KW - chromatographic fingerprinting KW - DAD KW - ED KW - herbal adulteration KW - MS. KW - Tribulus terrestris KW - UHPLC AB -

Background: Erectile dysfunction (ED) characterized by the inability to achieve or maintain erection during sexual activity, is a common disorder occurring in men. ED has many treatment options, either by medication or by improving the psychosocial well-being of a man. However, the embarrassment associated with consulting healthcare providers may be the reason for the shift towards easily procurable herbal supplements. Herbal supplements have seen an increas-ing demand in the western countries and are associated to be synonymous with ‘safe’. However, the latter is not always the case. The said supplements can be adulterated or fraudulent by ex-changed, which can lead to adverse effects or toxicity in the consumer. Tribulus terrestris (TT), subject of this thesis, is a plant that is frequently present in sexual enhancing herbal food sup-plements sold to treat ED.
Aim: The study developed a screening approach for TT using Ultra High Pressure Liquid Chro-matography- Diode-Array detector (UHPLC–DAD) and evaluated the presence of TT in 20 unknown illegal plant food supplements by using the developed fingerprinting method.
Method: UHPLC-DAD was used to obtain chromatographic fingerprints. The pure plant extract was screened and optimized to develop a suitable method to obtain a specific fingerprint. The suitability of the method was evaluated by preparing triturations of TT with herbal matrices in varying ratios (1/2, 1/5, 1/10, 1/15, 1/20). Twenty unknown samples were screened for TT and further confirmation was carried out by UH¨PLC-mass spectrometry
Results and conclusion: It was found and confirmed that 7 unknown samples showed the pres-ence of TT and more than half of it were confirmed for adulteration, i.e. adding TT without indication on the packaging.

PB - VUB CY - Brussels, Belgium ER - TY - JOUR T1 - Chromatographic fingerprinting for the detection of herbal adulteration and herbal fraud in plant food supplements JF - Macedonian Pharmaceutical Bulletin Y1 - 2022 A1 - Eric Deconinck A1 - Surbhi Ranjan KW - fingerprinting KW - illegal market KW - plant food supplements AB -

not applicable

VL - 68 CP - 2 M3 - 10.33320/maced.pharm.bull.2022.68.04.092 ER - TY - Generic T1 - chromatographic fingerprinting for the detection of herbal adulteration and herbal fraud in plant food supplements Y1 - 2022 A1 - Eric Deconinck A1 - Surbhi Ranjan KW - chromatographic fingerprinting KW - plant food supplements AB -

Plant food supplements (PFS) are gaining popularity in the western world due to the general trend of returning to natural and traditional products, but also the evolution towards self-medication, the questioning of allopathic medicines and the misperception that “natural” and “herbal” stand synonym for “safe” play a role (Rocha et al, 2016).

The popularity of PFS resulted in the development of a market offering a wide range of products, representing high profits. Unfortunately, this made these products also vulnerable for fraud and adulteration, especially when purchased via internet, an interesting platform for the trade in fraudulent products (Mosihuzzaman and Choudhary, 2008). In this context two possible health threats may occur: (a) the PFS does not contain the plant or herb declared on the packaging. This can be either due to falsification or fraud, or confounding. (b) adulteration, with the distinction between chemical adulteration and herbal adulteration. In the first case the PFS contains an active pharmaceutical ingredient (API), not claimed on the package, representing a serious health risk. In the second case the product contains active plants or herbs which are not claimed on the packaging, and are regulated or toxic.

This paper deals with the problem of herbal adulteration and herbal fraud, i.e. the absence of the claimed medicinal plant. Polymeric Chain Reaction (PCR) analysis is the golden standard for the detection and identification of a specific plant, but in case of adulteration, complex mixtures or the necessity of screening for a series of plants it can become more tedious (Ichim, 2019). Here an approach is presented based on chromatographic fingerprinting and chemometrics to perform a targeted screening for three and two regulated plants, often found in PFS for potency enhancement and slimming respectively. 

JF - CMAPSEEC 2022 PB - AMPSEEC CY - Ohrid, North-Macedonia CP - AMPSEEC ER - TY - JOUR T1 - Contents of Amoxicillin Drugs Dispensed in Goma, Democratic Republic of Congo JF - African Journal of Pharmaceutical Sciences Y1 - 2022 A1 - T.E. Busha A1 - De Braekeleer,K. A1 - Yaxin Tie A1 - Eric Deconinck A1 - N. P. Mitangala A1 - O Vandenberg A1 - Y Coppieters A1 - F. Vermeulen A1 - C. M. Harrison A1 - Byl, Baudouin KW - Content of Amoxicillin KW - Drugs dispensed in Goma KW - Quality of amoxicillin in DRC AB -

We studied 15 specimens of amoxicillin and 9 specimens of amoxicillin-clavulanic acid collected from pharmacies in Goma, DR Congo. Their claimed origin was India (n=11), DR Congo (n=5), France (n=4), Kenya (n=1), China (n=1), Germany(n=1), and Switzerland (n=1). The specimens were checked for falsifications following the WHO checklist. Content identity and amount of antibiotics in the specimens was investigated by Ultra High Performance Liquid Chromatography coupled with tandem mass spectrophotometry (UHPLC-MS/MS) and diode array detection (UHPLC-DAD). Nine of the 24 samples fulfilled the WHO criteria of counterfeit drugs, but all samples contained the active ingredients as claimed on the packages. We found under dosage of 90% and less in 3 of the 15 amoxicillin samples and in none of the 9 combined specimens. Amoxicillin over dosage (defined as 110% or more of indicated content) was found in 3 of the amoxicillin and in 1 of the combined specimens. Clavulanic acid was underdosed in none but overdosed in 5 of the 9 combined specimens. Our results highlight the need for drug quality control through inspection and specific analytical methods such as spectrophotometry and chromatography to reduce the public health challenge of illegal and substandard medicines in sub-Saharan Africa

VL - 2 CP - 1 M3 - https://doi.org/10.51483/AFJPS.2.1.2022.14-22 ER - TY - Generic T1 - Detection of regulated and prohibited plants in plant food supplements Y1 - 2022 A1 - Eric Deconinck AB -

Plant food supplements, herbal treatments and traditional medicines, bought via internet and intercepted by the authorities are often only screened for the presence of chemical adulterants like sibutramine and analogues in slimming preparations or sildenafil and analogues in potency enhancers. Other underestimated problems with these herbal preparations could also be herbal adulterations and herbal fraud. The first is the intentional presence of regulated or prohibited plants in the preparation, the latter is the absence of the claimed medicinal plant.

 

In Belgium the OMCL is regularly asked to perform analysis in this context, namely to identify/detect a certain plant in a herbal preparation, composed of a mixture of different plants.

For this purpose the OMCL is involved in two projects to tackle this problem. In the first a DNA metabarcoding approach is developed. In short DNA is extracted from the complex mixture, followed by next-generation sequencing and advanced bio-informatics in order to identify all plants present in the mixture. The second project focusses on the use of chromatographic fingerprints and chemometrics in order to recognize the chromatographic profile of the targeted plant in the mixture and classify it as positive or negative for the targeted plant.

 

For this first topic of the break-out session on herbals, the questions that are presented for discussion are:

  1. Are there other OMCLs occupied or interested in the problem of herbal adulteration? Did you receive already questions by courts or inspection in this context?
  2. What are the approaches followed in other OMCLs?
  3. What kind of analysis are performed on herbal products in your OMCL?
JF - Combating Counterfeit and Other Illegal Medicines: 4th Symposium for OMCLs: New trends, new frontiers PB - EDQM CY - Rome, Italy CP - EDQM ER - TY - JOUR T1 - Discrepancies between validated GC‐FID and UHPLC‐DAD methods for the analysis of Δ‐9‐THC and CBD in dried hemp flowers JF - Drug Testing and Analysis Y1 - 2022 A1 - Céline Duchateau A1 - Cedric De Leersnijder A1 - Sophia Barhdadi A1 - Michael Canfyn A1 - De Braekeleer, Kris A1 - Eric Deconinck KW - agricultural hemp KW - GC-FID KW - herbal product for smoking KW - UHPLC-DAD VL - 14 CP - 10 M3 - 10.1002/dta.3354 ER - TY - Generic T1 - E-sigaretten: kunnen de smaken je later zuur opbreken? Analyse van smaakstoffen in vloeistoffen voor e-sigaretten T2 - HuisartsNu Y1 - 2022 A1 - Sophia Barhdadi A1 - Tamara Vanhaecke A1 - Eric Deconinck KW - aerosol KW - roken JF - HuisartsNu PB - HuisartsNu VL - 51 UR - https://www.huisartsnu.be/2022/nr3/artikel/e-sigaretten-kunnen-de-smaken-je-later-zuur-opbreken-analyse-van-smaakstoffen CP - 3 ER - TY - JOUR T1 - European fingerprint study on omeprazole drug substances using a multi analytical approach and chemometrics as a tool for the discrimination of manufacturing sources JF - Journal of Pharmaceutical and Biomedical Analysis Y1 - 2022 A1 - H. Rebiere A1 - Y. Grange A1 - Eric Deconinck A1 - Patricia Courselle A1 - J. Acevska A1 - K. Brezovska A1 - J. Maurin A1 - T. Rundlöf A1 - M.J. Portela A1 - L.S. Olsen A1 - C. Offerlé A1 - M. Bertrand KW - Chemometrics KW - Data fusion KW - fingerprint KW - OMCL network KW - Omeprazole API KW - Substandard and falsified products AB -

Like drug products, Active Pharmaceutical Ingredients (APIs) are subject to substandard and falsification issues, which represent a threat to patient health. In order to monitor the quality of drug substances and prevent the use of non-compliant APIs, Official Medicine Control Laboratories work together in a European network developing coordinated strategies and programmes. The API working group proposed a market surveillance study on omeprazole and omeprazole magnesium with the objectives of controlling the pharmaceutical quality of samples, checking compliance with the monographs of the European Pharmacopoeia, and collecting analytical fingerprints that could be further used to differentiate manufacturing sources for future authenticity investigations. The study described in this article reports the analysis carried out by 7 European laboratories on 28 samples from 11 manufacturers with 5 analytical techniques (related substances with HPLC, residual solvents with GC-MS, near infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and X-ray powder diffractometry). The large amount of resulting analytical data were centralized and treated with two chemometric methods: Principal Component Analysis and Hierarchical Clustering Analysis. Data were analyzed separately and in combination (data fusion), allowing us to conclude that NMR and XRPD were suitable to differentiate samples originating from 9 out of 11 manufacturers. Analytical fingerprints associated with chemometrics were demonstrated to be a valuable methodology to discriminate manufacturers of omeprazole and omeprazole magnesium APIs and detect future substandard and falsified APIs.

VL - 208 M3 - 10.1016/j.jpba.2021.114444 ER - TY - Generic T1 - Feasibility study of using surface enhanced Raman scattering (SERS) combined with handheld Raman spectrometer for the detection of nicotine in e-liquids Y1 - 2022 A1 - Charlotte De Bleye A1 - Lise De Barsy A1 - Sophia Barhdadi A1 - Eric Deconinck A1 - Pierre-Yves Sacré A1 - Philippe Hubert A1 - Eric Ziemons JF - GFSV Nivelles 2022 PB - Groupe Français de Spectroscopie Vibrationnelle (GFSV) CY - Nivelles, Belgium CP - Groupe Français de Spectroscopie Vibrationnelle (GFSV) ER - TY - JOUR T1 - GEONs API fingerprint project: Selection of analytical techniques for clustering of sildenafil citrate API samples JF - Talanta Y1 - 2022 A1 - Eric Deconinck A1 - Patricia Courselle A1 - M. Raimondo A1 - Y. Grange A1 - H. Rebiere A1 - A. Mihailova A1 - O. Bøyum A1 - J.K. Maurin A1 - K. Pioruńska-Sędłak A1 - L. Stengelshøj Olsen A1 - J. Acevska A1 - K. Brezovska A1 - T. Rundlöf A1 - M.J. Portela A1 - M. Bertrand KW - APIs KW - fingerprint KW - GEON/OMCL network KW - illegal medicinal products KW - Sildenafil Citrate AB -

Through its Active Pharmaceutical Ingredient Working Group (API-WG) the General European Official Medicines
Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of
Medicines & HealthCare (EDQM), regularly organises market surveillance studies for specific APIs for conformity
to their monograph in the European Pharmacopoeia. During the past years some studies were combined with a
fingerprint study of the APIs. The idea is to obtain a fingerprint for each manufacturer of the API under investigation,
allowing the OMCL network to identify future samples as well as to detect substandard and falsified
APIs.
This paper reports the results of the latest fingerprint study, organised on sildenafil citrate API samples.
Seventy-nine samples from 14 different manufacturers were collected throughout the Network. Fingerprint data
was collected through Mid-Infrared spectroscopy, Raman spectroscopy, liquid chromatography for related substances,
gas chromatography for residual solvents, X-ray diffraction and Nuclear Magnetic Resonance (NMR)
spectroscopy. Chemometrics applied to the collected data showed that all manufacturers could be discriminated
based on the data of only three of these tests, i.e. gas chromatography for residual solvents, X-ray diffraction and
proton NMR. Suspicious API samples for sildenafil citrate will therefore be analysed in the future with the
selected techniques in order to link the sample to a manufacturer or demonstrate the absence of such link. If the
sample cannot be attributed to one of the manufacturers, further analysis and research on provenance and
identity will be required. Of course, if the suspected sample claims to originate from one of the manufacturers
included in the study, analysis can be limited to the test distinguishing this manufacturer.

VL - 239 M3 - 10.1016/j.talanta.2021.123123 ER - TY - Generic T1 - The GEONs API-fingerprint program: Tackling falsifications of APIs Y1 - 2022 A1 - Eric Deconinck KW - API KW - fingerprint KW - GEON AB -

Falsification of active pharmaceutical ingredients (APIs) has been recognized as an important health issue since a series of health scares involving large numbers of casualties happened when altered APIs escaped detection in routine analytical testing. Any form of tampering the content or information about the content might affect the quality of the API, the finished product and therefore constitutes a direct threat to the health of patients (Position paper for OMCLs on API surveillance, EDQM). The conventional analytical approach often fails to detect falsification since the quality and quantity of the API might be within the current standards. Instead, methods that allow distinction of API samples, according to their source are needed.

Within the General European Official Medicines Control Laboratory (OMCL) Network (GEON) different initiatives were taken to augment the analysis and market surveillance of APIs used by the different manufacturers. Despite the efforts, API testing within the network is limited, compared to the surveillance of finished products. To tackle the issue of falsified API detection the API-working group (API-WG) of the GEON organizes atypical market surveillance studies (MSS), where an MSS (analysis according to the Ph. Eur.) is combined with a fingerprint study (MSSFP). An MSS, according to Ph. Eur. only gives an indication of the quality of the product on some distinct parameters, often chosen based on the manufacturing process. A MSSFP study allows to obtain a global image of the sample, to compare to batches of the (presumed) manufacturer and/or to data of fingerprint studies performed in the past. (Deconinck et al., 2022, Rebiere et al., 2022).

The aim of the paper is to highlight the challenges and pitfalls in detecting falsified APIs and to give an insight in the work of the GEONs API-WG with a special focus on the MSSFP studies. A summary is given of the MSSFP study on sildenafil citrate and this for the set-up and the obtained results.  

JF - 7th Congress of Pharmacy in North-MAcedonia PB - AMP CY - Ohrid, North-Macedonia CP - MPA ER - TY - JOUR T1 - The GEONs API-fingerprint program: tackling falsifications of APIs JF - Macedonian Pharmaceutical Bulletin Y1 - 2022 A1 - Eric Deconinck KW - API KW - fingerprinting KW - GEON AB -

not applicable

VL - 68 CP - suppl 1 M3 - 10.33320/maced.pharm.bull.2022.68.03.010 ER - TY - Generic T1 - Identification of flavouring substances of genotoxic concern in e-liquids Y1 - 2022 A1 - Sophia Barhdadi A1 - Vanhaecke, Tamara A1 - Birgit Mertens A1 - Eric Deconinck KW - e-cigarette KW - genotoxicity JF - BfR Consumer Protection Forum "Opportunities and Risks of the e-cigarette" PB - BfR CY - Berlin, Germany ER - TY - Generic T1 - Multidimensional Fingerprint Development for the Detection of Tribulus terrestris in Plant Food Supplements Y1 - 2022 A1 - Surbhi Ranjan A1 - Sano-Magnifique Dusingizimana A1 - Tanika Van Mulders A1 - Eric Deconinck A1 - Erwin Adams KW - Fingerprints KW - plant food supplements KW - Tribulus terrestris AB -

Tribulus terrestris is a popular Ayurvedic herb with potency enhancing properties. According
to the Belgian Royal Decree of 1997, Tribulus is a regulated plant when used in plant food
supplements. The dangers of self-medication and toxicity of such plant supplements is
heightened by the ease with which they can be purchased from various illegal channels,
necessitating an efficient screening approach.
This study aims to develop a multidimensional approach using chromatographic fingerprinting
at different wavelengths for identification of Tribulus terrestris in plant food supplements. A
specific, selective and fast fingerprinting method for Tribulus (reference material obtained from
the American Herbal Pharmacopoeia) was developed using ultra high performance liquid
chromatography coupled with a diode array detector. Next, a correlation analysis comparing
the wavelengths was performed and 5 orthogonal wavelengths were selected. The developed
method was tested for specificity in different triturations (1/20, 1/15, 1/10, 1/5 and 1/2). These
were prepared using 10 blank matrices and lactose. In most triturations, Tribulus could visually
be detected from concentration 1/10 onwards, by comparing the fingerprints with the reference
plant.
A market study of a total of 20 samples (with potency enhancement as indication) seized by
the Belgian Federal Agency for Medicines and Health Products (FAMHP) was carried out.
Visual inspection was conducted to detect the presence of Tribulus in the real samples. This
was done by overlaying the sample chromatograms with the reference plant and visually
comparing the fingerprints. So, out of 20 samples, 11 samples were suspected to be positive,
when analyzed at the 5 wavelengths, 254 nm and with the combined fingerprint. The multi and
combined wavelengths approach provides a characteristic and specific fingerprint with more
information at different wavelengths than only 254 nm, which is useful for visual inspection. In
a second step, mass spectrometric (MS) measurements using a time of flight analyzer were
performed. This was done in order to further confirm the presence of Tribulus in suspected
samples. After obtaining MS fingerprints, the exact mass of the main peaks (peaks with the
highest absorbance in the reference) were compared. It was concluded that out of 11 samples,
9 can be suspected to be positive for Tribulus terrestris. As future prospects, steps are being
taken to combine chromatographic fingerprinting and chemometrics in order to use these
multidimensional data and extract maximum information with the intention to create binary
models for faster screening of plant food supplements.

JF - Drug Analysis PB - Drug Analysis CY - Mons, Belgium CP - BSPS, UMons, ULB ER - TY - JOUR T1 - The purity of tattoo inks, screening substances of high concern JF - Regulatory Toxicology and Pharmacology Y1 - 2022 A1 - Bart Desmedt A1 - Melissa Vanhamme A1 - Eric Deconinck KW - Ink KW - Primary aromatic amines KW - Risk Assessment KW - SCREENING KW - Tattoo AB -

nowadays. Currently, there is no harmonized legislation in Europe but from 2022 on, tattoo inks will be regulated
through a REACH Amendment implementing compound-specific restrictions.
Methodology: A screening method based on LC-QqQ-MS was developed and validated for screening 40 substances
of high concern in tattoo inks. An additional quantification method was validated to quantify 5-nitro toluidine
and 4-chloroaniline in tattoo inks with high accuracy. The method was validated according to the total error
approach with an acceptance value of ±20%
Results: The methodology was applied to 86 samples of which 26 are violating the current Resolution ResAP
(2008). 5-nitro toluidine was found in 16 samples, all of them having an unacceptable health risk, with an
average concentration of 29 μg/g basic violet 10, basic red 1, 4-chloroaniline, and basic red 9 were detected 8, 7,
4, and 3, times respectively. Counterfeit products with lower quality were observed.
Conclusion: Our results show that low-quality tattoo inks are easily available to the European consumer. In line
with literature, most infringements were observed with red/brown inks which is not surprising since these colors
are most often associated with adverse health effects.

VL - 129 M3 - 10.1016/j.yrtph.2022.105123 ER - TY - JOUR T1 - Quantitative risk assessment of allergens leaching from menstrual hygiene products. JF - Regul Toxicol Pharmacol Y1 - 2022 A1 - Quinten Marcelis A1 - Alexandra Gatzios A1 - Eric Deconinck A1 - Rogiers, Vera A1 - Vanhaecke, Tamara A1 - Bart Desmedt KW - Allergens KW - Dermatitis, Allergic Contact KW - Female KW - Humans KW - Hygiene KW - Menstrual hygiene products KW - Menstruation KW - Risk Assessment AB -

Allergic contact dermatitis (ACD) often associated with the topical use of perfumed products, remains one of the most common chronic skin disorders in Western countries. Since labelling of scented menstrual hygiene products (MHPs) is not mandatory, women might be unknowingly exposed to allergens. Given that vaginal mucosae lack the vital barrier function of the skin, skin allergens can easily penetrate and become systemically available and hence women may experience adverse effects in the anogenital region. The aim of this study was therefore to investigate whether women using scented MHPs are at risk of sensitization and hence developing ACD. Hereto, a Quantitative Risk Assessment (QRA) is performed on four well-known skin sensitizing chemicals (α-isomethyl ionone, benzyl salicylate, hexyl cinnamaldehyde and heliotropine) that were previously found leaching from five different scented MHPs including tampons and sanitary pads. The amounts of heliotropine, leached by one of the investigated tampons, exceeded acceptable exposure levels determined with the QRA and could induce sensitization. In addition, although no sensitization is expected for the other three compounds, an allergenic reaction might be provoked in women who are already sensitized. Labelling of allergens on scented MHPs would therefore help consumers to prevent adverse effects linked to ACD.

VL - 135 M3 - 10.1016/j.yrtph.2022.105260 ER - TY - JOUR T1 - Relative response factors and multiple regression models in liquid chromatography to quantify low-dosed components using alternative standards-proof of concept: total Δ9-THC content in cannabis flowers using CBD as reference. JF - Anal Bioanal Chem Y1 - 2022 A1 - Cedric De Leersnijder A1 - Céline Duchateau A1 - De Braekeleer, Kris A1 - Eric Deconinck KW - Cannabinoids KW - cannabis KW - Chromatography, Liquid KW - Dronabinol KW - Flowers KW - Hallucinogens KW - Reference Standards AB -

A classical quantitative analysis in liquid chromatography is performed using either a one-point calibration or a calibration line, prepared using a reference standard of the compound(s) of interest. However, in some cases, adequate reference standards may be very expensive, rare to obtain, or have limited shelf-life properties. Also, in herbal matrices, multiple compounds could be necessary to be quantified, needing a whole series of different (related) reference standards. In these cases, the use of relative response (sometimes called relative correction factors) factors (RRFs) towards reference standards, different of the compound to be quantified, gained attraction. This study performed a comparison of the use of RRFs and linear relative response factor models (LRRFM) for the quantification of targeted low-dosed compounds using an alternative standard, since it is known that classical RRFs often fail in lower concentration ranges. For this purpose, the determination of the total Δ9-tetrahydrocannabinol (Δ9-THC + Δ9-THC-A) content in dried cannabis flowers, using UHPLC-DAD, was used as a case study. A chromatographic method was implemented and validated, and the use of classical calibration lines, classical RRF, and the LRRFM was applied and compared, with special focus on the concentration around 0.2% (w/w) total Δ9-THC, the legal limit (in most European countries) in these products. Results showed that the newly presented and validated LRRFM approach outperformed the classical RRFs, especially in the low-concentration ranges and that concentrations obtained with the LRRFM were in accordance with the interpolation results obtained with a calibration line.

VL - 414 CP - 22 M3 - 10.1007/s00216-022-04208-y ER - TY - Generic T1 - Use of near infrared spectroscopy and chemometrics for the classification of different Cannabis spp. samples found in Belgium Y1 - 2022 A1 - Céline Duchateau A1 - Kauffmann, Jean-Michel A1 - Michael Canfyn A1 - Kris de Braeckeleer A1 - Eric Deconinck AB -
  1. Introduction

Cannabis is known for a variety of applications e.g. . in the textile industry but more importantly for recreational and medical use. Cannabis and its derived products are available on the Belgium market via both illegal and legal ways. CBD flowers as well as medicinal cannabis can both be purchased in a legal way, but cannabis to be used as recreational drug is illegal. Indeed, cannabis is the most widely consumed illicit drug in Europe and products contain generally a concentration of Δ9-THC up to 15 %  (m/m) [1,2]. Δ9-tetrahydrocannabinol is one of the main cannabinoids responsible for the psychotropic effects and the Belgian law authorizes a maximal concentration of 0.2 % (m/m) [2]. However, there are only limited cannabis seizures because it is difficult to discriminate between legal CBD flowers and cannabis flowers with a Δ9-THC concentration higher than 0.2% m/m, at least for police officers on site. There is a need to characterize these products with a rapid, ecological and cheap analytical method. The current methods of reference are GC-MS, GC-FID and HPLC-DAD [4]. These methods are very efficient but slow, expensive and require a thorough sample preparation. Furthermore, they require trained personnel, and aren’t ecological [4,5] and they are not suited for onsite analysis. Near infrared spectroscopy combined with chemometric tools has the potential for quantitative and qualitative prediction of plant natural products compounds [6]. In addition, near infrared spectroscopic tools are easy to employ, green, rapid and relatively cheap and can be used on-site (handheld devices).

 

  1. Material and methods

For this study 189 samples, found in Belgium, were used. They were composed of (i) flowers seized on festivals and on the street and supplied by the Belgian authorities, (ii) agricultural hemp from Belgian farmers and (iii) flowers, used or sold as “other tobacco to smoke”, either seized by Belgian authorities, bought on the Belgium market or voluntarily donated by sellers in order to analyze their samples.

Cannabis samples were analyzed by GC-FID for total-tetrahydrocannabinol detection and quantification with an officially validated method.

The analysis of these products was performed by FT-NIR spectrometer (spectra were recorded in  reflectance mode with the Near Infrared Reflectance Accessory (NIRA)) and dispersive NIR handheld devices combined with chemometrics. 

All pretreated spectra were analysed with chemometrics. Principal component analysis (PCA) is applied as exploratory data analysis. Soft independent modelling of class analogy (SIMCA) was used to build a binary classification model according to the Belgian legislation.

All chemometric treatments were performed with Matlab R2018b (The Mathworks®). The algorithms were part of the ChemoAC toolbox (Freeware®, ChemoAC consortium, version 4.1).

  1. Results and discussion

 

Figures : Score plot of the PC1, PC2 and PC3 of spectra pretreated. Samples with >0.2% THC in red and blue and sample with < 0.2% THC in green.

The SIMCA classification model has a correct classification rate of 92 % (for the benchtop) and 93 % (for the handheld device),  meaning that 51 of the 56 samples and 52 of 56 samples in the external test set are correctly classified as recreational drug, industrial hemp or cannabis flowers containing less than 0.2% m/m of Δ9-THC.

  1. Conclusion

Near infrared spectroscopy allows to discriminate various samples. The difference is caused by the totality of compounds of the plant and not only by the Δ9-THC content. Indeed, plant material is a complex matrix and the fingerprint is a combination of the totality of compounds. This preliminary study is a first step to prove that NIR spectroscopy could be used as a preliminary screening method for the authorities to make the decision to seize or not.

JF - Combating Counterfeit and Other Illegal Medicines: 4th Symposium for OMCLs: New trends, new frontiers PB - EDQM CY - Rome, Italy CP - EDQM ER - TY - JOUR T1 - Analytical characterization of "etonitazepyne," a new pyrrolidinyl-containing 2-benzylbenzimidazole opioid sold online. JF - Drug Test Anal Y1 - 2021 A1 - Peter Blanckaert A1 - Margot Balcaen A1 - Celine Vanhee A1 - Martijn Risseeuw A1 - Michael Canfyn A1 - Bart Desmedt A1 - Van Calenbergh, Serge A1 - Eric Deconinck KW - Benzimidazoles KW - etonitazene KW - new psychoactive substances KW - opioid NPS KW - pyrrolidine analogue AB -

This paper reports on the identification and full chemical characterization of the substance colloquially called "etonitazepyne" or "N-pyrrolidino etonitazene" (2-(4-ethoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole), a potent NPS opioid of the 5-nitrobenzimidazole class. Identification of etonitazepyne was performed, on a sample purchased during routine monitoring of the drug market, using GC-MS, HRAM LC-MS/MS, H NMR, and FTIR. The chromatographic data, together with the FTIR data, indicated the presence of a highly pure compound and already indicated a benzimidazole structure. The specific benzimidazole regio-isomer was confirmed using H NMR spectroscopy, resulting in the unambiguous identification of etonitazepyne.

VL - 13 CP - 9 M3 - 10.1002/dta.3113 ER - TY - JOUR T1 - CBD oils on the Belgian market: A validated MRM GC-MS/MS method for routine quality control using QuEChERS sample clean up JF - Journal of Pharmaceutical and Biomedical Analysis Y1 - 2021 A1 - Céline Duchateau A1 - Michael Canfyn A1 - Bart Desmedt A1 - Kauffmann, Jean-Michel A1 - Stévigny, Caroline A1 - De Braekeleer, Kris A1 - Eric Deconinck KW - Cannabidiol KW - CBD oils KW - GC-MS/MS KW - MRM KW - Sample clean up AB -

Quality control of CBD oils on the Belgium market showed that the CBD content not always corresponds to the label claim. There is a pressing need to develop new analytical methods specifically developed to the assay of such oily samples. Analytical issues are, however, encountered for routine analyses due to the matrix complexity, high cost of cannabinoid standards and low Δ9-THC concentrations. An oily matrix could cause technical damages to analytical instruments and reduce the lifetime of the chromatographic columns. This paper proposes a procedure combining a sample cleanup by QuEChERS, removing the oily matrix, followed by a validated MRM GC-MS/MS method for the routine analysis of CBD oil samples. Eighteen CBD samples were selected on the Belgium market for analysis. This method allows the quantification of CBD, the legality check for the Δ9-THC content by a CBN standard and the screening of seven other cannabinoids namely CBN, CBDV, CBT, CBC, Δ8-THC, THCV and CBG. The method was validated at three concentration levels (0.5–1–2% (w/v)) for CBD and (0.05–0.1–0.2% (w/v)) for CBN. The detection limits for CBT, CBD, CBC, Δ8-THC, CBN and for the other cannabinoids of interest, were 10 and 14 ng/mL respectively. The accuracy profile values for CBD and CBN showed that the β-expectation tolerance intervals did not exceed the acceptance limits of 20%, meaning that 90% of future measurements will be included within this error range.

VL - 205 M3 - 10.1016/j.jpba.2021.114344 ER - TY - Generic T1 - Characterization and risk identification of falsified medicines and adulterated dietary supplements Y1 - 2021 A1 - Eric Deconinck A1 - Yaxin Tie A1 - Surbhi Ranjan A1 - Celine Vanhee KW - Illegal medicines AB -

Characterization and risk identification of falsified medicines and adulterated

dietary supplements

 

Both the increasing occurrence of illegal and substandard medicines and adulterated dietary supplements or traditional medicines represent a treat to global public health.

A recent research project, financed by a scholarship of the Chinese Research Council (2016-2020), focused on the identification of the risks associated with the use of Illegal antibiotics. In this project, more than fifty seized samples were evaluated for their chemical, galenic and microbial quality, showing failures for impurity content, dissolution and microbial purity (presence of neurotoxin producing fungi). This project showed clearly that chemical quality of illegal medicines is not enough to evaluate their risk and that a broader characterization of the products is necessary for a correct risk evaluation. In another part of the project an onsite infrared based approach was developed for a first quality check of illegal antibiotics at e.g. customs.

The chemical adulteration of dietary supplements is a well-known and well documented problem in literature, but an underestimated problem is the Herbal adulteration of Plant Food Supplements (PFS) and herbal or traditional medicines. Our service works on the innovative application of chromatographic fingerprints, combined with chemometrics to detect prohibited or regulated plants in herbal mixtures. In a new project the service is turning towards multi-dimensional fingerprints and mass spectrometry fingerprints in order to augment selectivity and specificity for the detection of targeted plants in mixtures.

It stands to reason that collaborations on these topics would be beneficial for both the European and the Chinese policy makers to tackle this common threat, but also to protect the reputation of the pharmaceutical industry and the Traditional medicines in both regions. These collaborations can go from collaborative PhD projects (financed by one of the respective national bodies) over joint applications for research grants (Belspo, European commission, …) to joint labs and infrastructures, between the respective competent authorities for the development of analytical strategies, risk evaluation, standardisation of analytical methodologies (e.g. common monographs between the respective Pharmacopoeia)., etc. 

 

 
 

JF - 2nd China-Belgium Innovation Dialogue CY - Online meeting CP - MOST-BELSPO ER - TY - JOUR T1 - Development and application of a novel method to assess exposure levels of sensitizing and irritating substances leaching from menstrual hygiene products JF - Emerging Contaminants Y1 - 2021 A1 - Quinten Marcelis A1 - A. Gatzios A1 - Eric Deconinck A1 - Rogiers, V. A1 - Vanhaecke, T. A1 - Bart Desmedt KW - Consumer Product Safety KW - Fragrance KW - Menstrual hygiene products KW - Skin irritation KW - Skin sensitization AB -

Menstrual hygiene products (MHPs) like tampons, sanitary towels and panty liners are widely used by women and come in close contact with the intimate parts of the human body, which consist of mucosae that lack the important barrier function of normal skin. Hence, substances leaching from MHP can easily penetrate and become systemically available. This study aims to develop a new in chemico methodology that allows to identify and measure realistic consumer exposure levels of several skin sensitizers and irritants leaching from MHPs under simulated use conditions. To assess the leaching of chemicals from MHPs, a menstrual fluid simulant (MFS) simulating pH, osmolarity and protein binding was first established. Subsequently, an analytical methodology was developed for nine well-known skin sensitizers and skin irritants. In short, the MFS samples underwent salting-out assisted liquid-liquid extraction before ultra-high performance liquid chromatography coupled with a triple-quadrupole mass spectrometry analysis. Validation was performed according to the total error approach with acceptability limits of ±15% regarding the total analytical error (including systematic and random bias). Fifteen commercially available MHPs were assessed. Six products were found to leach at least one of the following five sensitizing and irritating compounds: α-isomethyl ionone, benzyl salicylate, hexyl cinnamaldehyde, linalool and piperonal. Piperonal was the most abundant compound leaching from the MHPs, with leaching concentration levels measured to 28.22 μg/g. In addition, the leaching level of benzyl salicylate was found to be 11.03 μg/g. The latter fragrance concentration is above 10 μg/g and would trigger mandatory labelling if the Cosmetic Regulation would apply for MHPs. However, none of the identified and quantified skin sensitizers were mentioned on the packaging. In conclusion, this novel methodology makes it possible to estimate realistic human exposure levels to skin sensitizers and irritants through the use of MHPs. Availability of these exposure estimates is vital to carry out a quantitative health risk assessment of these substances.

VL - 7 M3 - 10.1016/j.emcon.2021.02.004 ER - TY - JOUR T1 - Development of a “Freeze-Pour” Sample Preparation Method for the GC Analysis of Semivolatile Flavouring Chemicals Present in E-cigarette Refill Liquids JF - LCGC Europe Y1 - 2021 A1 - Sophia Barhdadi A1 - Michael Canfyn A1 - Sanae El Merabety A1 - Patricia Courselle A1 - Rogiers, Vera A1 - T Vanhaecke A1 - Eric Deconinck KW - e-cigarettes KW - flavours KW - GC-MS KW - genotoxicity AB -

During the past decade, e-cigarettes have become increasingly popular. To guarantee their safe use and to comply with the notification requirements of the EU Tobacco Product Directive, the EU member state regulatory authorities need information about the exact composition of the e-liquids and their emissions. However, one of the challenges encountered during the analysis of e-liquids is the presence of the highly abundant e-liquid matrix components propylene glycol and glycerol. In this study, headspace gas chromatography (HS-GC) analysis is presented as an excellent method for the analysis of high volatile components in e-liquids. For the analysis of semivolatile ingredients, an additional sample preparation step is proposed based on a liquid–liquid extraction (LLE) followed by a freeze-out of the matrix components. The developed method was successfully validated in accordance with the validation requirements of ICH guidelines for the quantification of four flavourings with a potential health concern for e-cigarette users.

VL - 34 CP - 6 M3 - https://www.chromatographyonline.com/view/development-of-a-freeze-pour-sample-preparation-method-for-the-gc-analysis-of-semivolatile-flavouring-chemicals-present-in-e-cigarette-refill-liquids ER - TY - JOUR T1 - Energy Drink Consumption among Adolescents Attending Schools in Lubumbashi, Democratic Republic of Congo. JF - Int J Environ Res Public Health Y1 - 2021 A1 - Trésor Carsi Kuhangana A1 - Taty Muta Musambo A1 - Joseph Pyana Kitenge A1 - Tony Kayembe-Kitenge A1 - Arlène Kazadi Ngoy A1 - Paul Musa Obadia A1 - Banza Lubaba Nkulu, Célestin A1 - Angelique Kamugisha A1 - Eric Deconinck A1 - Nemery, Benoit A1 - Joris Van Loco KW - ADOLESCENT KW - Child KW - cross-sectional studies KW - Democratic Republic of the Congo KW - Energy Drinks KW - Female KW - Humans KW - Male KW - Schools KW - Surveys and Questionnaires AB -

BACKGROUND: The consumption of energy drinks (EDs) is increasing in the general population, but little is known about the consumption of EDs among pupils in Africa. This study was designed to assess the consumption of EDs among pupils between 10 and 17 years of age and to assess average caffeine concentrations contained in EDs sold in Lubumbashi.

METHODS: We conducted a cross-sectional survey in five schools using a standardised questionnaire taken face-to-face. Samples of locally purchased EDs were analysed by High Performance Liquid Chromatography with Ultra-Violet spectrometry (HPLC-UV).

RESULTS: Of 338 pupils (54% girls), 63% reported having consumed at least one ED in the last week and 34% drank at least one ED a day. The cheapest ED was the most widely consumed. Among pupils having consumed at least one ED in the last week, 79% reported consuming it for refreshment and 15% to get energy. For those who reported not consuming EDs, 40% reported that their parents or teachers forbade them to drink EDs. Some (14%) teenagers, mainly boys, mixed ED with alcohol. The concentrations of caffeine measured in twelve brands of EDs ranged from 7.6 to 29.4 mg/100 mL (median 23.3), giving caffeine contents of 37.5 to 160 mg (median 90 mg) per can or bottle. The estimated daily intake of caffeine through EDs was between 51.3 mg and 441.3 mg among those consuming EDs regularly.

CONCLUSION: Our study convincingly demonstrates that caffeine-containing EDs are not only consumed by youngsters living in affluent societies. We documented widespread regular consumption of EDs among (pre-)adolescent schoolchildren living in Lubumbashi, a large city of the Democratic Republic of Congo (DRC). In view of the global market expansion of caffeinated EDs, it is reasonable to suspect that similar surveys in other urban areas of sub-Saharan Africa would yield similar findings. Pricing and advertising regulations and education on EDs are necessary to limit the regular consumption of EDs among adolescents.

VL - 18 CP - 14 M3 - 10.3390/ijerph18147617 ER - TY - JOUR T1 - Identification of flavouring substances of genotoxic concern present in e-cigarette refills JF - Food and Chemical Toxicology Y1 - 2021 A1 - Sophia Barhdadi A1 - Birgit Mertens A1 - Melissa Van Bossuyt A1 - Jolien Van de Maele A1 - Roel Anthonissen A1 - Michael Canfyn A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Eric Deconinck A1 - Vanhaecke, Tamara KW - (Q)SAR methodologies KW - e-cigarettes KW - genotoxicity KW - mutagenicity AB -

E-cigarettes have become very popular, a trend that has been stimulated by the wide variety of available e-liquid flavours. Considering the large number of e-liquid flavours (>7000), there is an urgent need to establish a screening strategy to prioritize the flavouring substances of highest concern for human health. In the present study, a prioritization strategy combining analytical screening, in silico tools and literature data was developed to identify potentially genotoxic e-liquid flavourings. Based on the analysis of 129 e-liquids collected on the Belgian market, 60 flavourings with positive in silico predictions for genotoxicity were identified. By using literature data, genotoxicity was excluded for 33 of them whereas for 5, i.e. estragole, safrole, 2-furylmethylketon, 2,5-dimethyl4-hydroxyl-3(2H)-furanone and transhexanal, there was a clear concern for in vivo genotoxicity. A selection of 4 out of the remaining 22 flavourings was tested in two in vitro genotoxicity assays. Three out of the four tested flavourings induced gene mutations and chromosome damage in vitro, whereas equivocal results were obtained for the fourth compound. Thus, although there is a legislative framework which excludes the use of CMR compounds in e-liquids, flavourings of genotoxic concern are present and might pose a health risk for e-cigarette users.

VL - 147 CP - 111864 M3 - 10.1016/j.fct.2020.111864 ER - TY - JOUR T1 - Impact of the revised European Tobacco Product Directive on the quality of e-cigarette refill liquids in Belgium JF - Nicotine & Tobacco Research Y1 - 2021 A1 - Sophia Barhdadi A1 - Moens, Goedele A1 - Michael Canfyn A1 - Celine Vanhee A1 - Bart Desmedt A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Vanhaecke, Tamara A1 - Eric Deconinck KW - e-cigarettes AB -

Introduction

Since its introduction, the e-cigarette has become a commonly used consumer product. In this study, we investigate whether regulatory changes had an impact on the quality of refill liquids (e-liquids) available on the Belgian market through analysis of their chemical composition. Hence, the nicotine concentration accuracy was investigated in samples before, during and after the implementation of the revised Tobacco Product Directive (TPD) as an indicator of good manufacturing practices. This is, however, not enough to assure the quality. Therefore, extra criteria were also assessed based on TPD requirements.

Methods

By using in-house validated methods, a total of 246 e-liquids purchased prior (2013-2015), during (2016) and after (2017-2018) the implementation of the TPD revisions, were analyzed for the presence of nicotine, nicotine-related impurities, volatile organic compounds (VOCs), caffeine and taurine, and the flavours diacetyl and acetylpropionyl.

Results

Although not all manufacturers managed to produce and label their products accurately, nicotine labelling discrepancies have decreased over time. Moreover, also the number of e-liquids, containing high risk VOCs (10% in 2016 versus none of the samples in 2017-2018), caffeine (16% in 2017 versus 5% in 2018) and diacetyl and acetylpropionyl (55% in 2017 versus 27% in 2018 of sweet flavoured samples) diminished over time.

Conclusion

Our results demonstrate that the overall quality of the e-liquids has improved after the implementation of the revised TPD. However, the results also show that periodic quality control might be required to ensure further compliance to the TPD.

Implications

This study clearly demonstrates that the implementation of the revised TPD has improved the quality of the e-liquids on the Belgian market. However, there are still e-liquids that are not in agreement with the TPD due to nicotine concentration label discrepancies, presence of e-liquid impurities and controversial flavours diacetyl and acetylpropionyl or the additive caffeine.

M3 - 10.1093/ntr/ntaa023 ER - TY - JOUR T1 - An infrared spectroscopic approach to characterise white powders, easily applicable in the context of drug checking, drug prevention and on-site analysis JF - Drug Testing and Analysis Y1 - 2021 A1 - Eric Deconinck A1 - Camille Ait-Kaci A1 - Andries Raes A1 - Michael Canfyn A1 - Bothy, Jean-Luc A1 - Céline Duchateau A1 - Corenthin Mees A1 - Kris de Braeckeleer A1 - L. Gremeaux A1 - Peter Blanckaert KW - ATR-(N)IR KW - Chemometrics KW - illicit drugs KW - Mobile detection approaches AB -

More and more events, such as the summer music festivals, are considering the

possibilities for implementing on-site testing of psychoactive drugs in the context of

prevention and harm reduction. Although the on-site identification is already

implemented by plenty of drug checking services, the required rapid quantitative

dosing of the composition of illicit substances is still a missing aspect for a successful

harm reduction strategy at events. In this paper, an approach is presented to identify

white powders as amphetamine, cocaine, ketamine or others and to estimate the

purity of the amphetamine, cocaine and ketamine samples using spectroscopic

techniques hyphenated with partial least squares (PLS) modelling. For identification

purposes, it was observed that mid-infrared spectroscopy hyphenated with

PLS-discriminant analysis allowed the distinction between amphetamine, cocaine,

ketamine and other samples and this with a correct classification rate of 93.1% for an

external test set. For quantitative estimation, near-infrared spectroscopy was more

performant and allowed the estimation of the dosage/purity of the amphetamine,

cocaine and ketamine samples with an error of more or less 10% w/w. An easily

applicable, practical and cost-effective approach for on-site characterisation of the

majority of the psychoactive samples encountered in Belgian nightlife settings based

on IR spectroscopy was proposed.

CP - 13 M3 - https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/dta.2973 ER - TY - JOUR T1 - The occurrence of non-anatomical therapeutic chemical-international nonproprietary name molecules in suspected illegal or illegally traded health products in Europe: A retrospective and prospective study. JF - Drug Test Anal Y1 - 2021 A1 - Eric Deconinck A1 - Celine Vanhee A1 - Peter Keizers A1 - Pauline Guinot A1 - Albena Mihailova A1 - Per Vidar Syversen A1 - Graziella Li-Ship A1 - Steven Young A1 - Agata Blazewicz A1 - Magdalena Poplawska A1 - Josephine Loasby Al-Sayed A1 - Lone Stengelshøj Olsen A1 - Oliver El-Atma A1 - Roman Leist A1 - Karl-Henrik Jönsson A1 - Maria Afxentiou A1 - M Barrios Mendoza A1 - Diaz, I Dorronsoro A1 - Marina Zemser A1 - Alla Kozokin A1 - Andreas Hackl A1 - Maria-Jao Portela A1 - Nico Beerbaum A1 - Marie Bertrand KW - GEON/OMCL network KW - illegal medicinal products KW - non-ATC-INN drugs AB -

The General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies on specific categories of suspected illegal or illegally traded products. These studies are generally based on a combination of retrospective and prospective data collection over a defined period of time. This paper reports the results of the most recent study in this context with the focus on health products containing non-Anatomical Therapeutic Chemical-International Nonproprietary Name (ATC-INN) molecules. In total 1104 cases were reported by 16 countries for the period between January 2017 and the end of September 2019. The vast majority of these samples (83%) were collected from the illegal market, while only 3% originated from a legal source. For the rest of the samples, categorisation was not possible. Moreover, 69% of all the reported samples were presented as medicines, including sexual performance enhancers, sports performance enhancers, physical performance enhancers and cognitive enhancers or nootropic molecules that act on the central nervous system (CNS). Although the popularity of anabolics, PDE-5 inhibitors and CNS drugs in illegal products has already been reported, the study showed some new trends and challenges. Indeed, 11% of the samples contained molecules of biological origin, that is, research peptides, representing the second most reported category in this study. Furthermore, the study also clearly shows the increasing popularity of Selective Androgen Receptor Modulators and nootropics, two categories that need attention and should be further monitored.

VL - 13 CP - 4 M3 - 10.1002/dta.3001 ER - TY - JOUR T1 - Report on a New Opioid NPS: Chemical and In Vitro Functional Characterization of a Structural Isomer of the MT-45 Derivative Diphenpipenol. JF - J Anal Toxicol Y1 - 2021 A1 - Annelies Cannaert A1 - Fabian Hulpia A1 - Martijn Risseeuw A1 - Katleen Van Uytfanghe A1 - Eric Deconinck A1 - Van Calenbergh, Serge A1 - Peter Blanckaert A1 - Stove, Christophe KW - Analgesics, Opioid KW - Chromatography, High Pressure Liquid KW - Designer Drugs KW - Gas Chromatography-Mass Spectrometry KW - illicit drugs KW - Piperazines AB -

In this paper, the identification and full characterization of a novel non-fentanyl opioid sourced online, which is a member of the 1-substituted-4-(1,2-diphenylethyl)piperazine derivatives related to MT-45, is reported. The sample was sold under the name "diphenpipenol," (3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylethyl]phenol), although extensive NMR analysis showed that the product obtained was actually a diphenpipenol structural isomer, (2-[4-(2-methoxyphenyl)piperazin-1-yl]-1,2-diphenylethanol). Liquid chromatography time-of-flight mass spectrometry identified an exact mass for the protonated molecule of m/z 389.2264, with two prominent fragment ions (m/z 91.0567 and 150.0937), which were not reported in earlier literature describing MT-45 derivatives. The chemical characterization was finalized by gas chromatography-mass spectrometry, high-performance liquid chromatography diode array detector and Fourier-transform infrared spectroscopy analyses. This product is a clear example of the trend that new non-fentanyl opioids are reappearing on the recreational drug market to escape the recent changes in (inter)national legislation concerning fentanyl analogues. Although in this particular case, the product's potency and efficacy were relatively low, other new non-fentanyl opioids might possess stronger potencies and therefore pose greater health risks for ignorant users. The fact that the product was sold under the wrong name further demonstrates the well-known problematic issue of a mismatch between the adverted and true identity, confirming the irregularities of the online new psychoactive substances market.

VL - 45 CP - 2 M3 - 10.1093/jat/bkaa066 ER - TY - JOUR T1 - Toxicity assessment of flavour chemicals used in e-cigarettes: current state and future challenges JF - Archives of Toxicology Y1 - 2021 A1 - Sophia Barhdadi A1 - Rogiers, Vera A1 - Eric Deconinck A1 - Vanhaecke, Tamara KW - e-cigarettes KW - flavours KW - toxicity AB -

NA

VL - 95 CP - 8 M3 - 10.1007/s00204-021-03080-6 ER - TY - RPRT T1 - Advies nr 9538. Nieuwe tabaksproducten: heated tobacco products Y1 - 2020 A1 - Frank Baeyens A1 - Pierre Bartsch A1 - Martial Bodo A1 - Hedwig Boudrez A1 - Eric Deconinck A1 - Heidi Demaegdt A1 - Suzanne Gabriels A1 - Stefaan Hendrickx A1 - Nackaerts, Kristiaan A1 - Pussemier, Luc A1 - Nicolas Van Larebeke-Arschodt PB - Hoge Gezondheidsraad ER - TY - JOUR T1 - Awareness of users and motivational factors for using new psychoactive substances in Belgium JF - Harm Reduction Journal Y1 - 2020 A1 - Simons,K. A1 - Michael Canfyn A1 - Anton Van Dijck A1 - Tina Van Havere A1 - Eric Deconinck A1 - Peter Blanckaert A1 - L. Gremeaux VL - 17 CP - 1 M3 - 10.1186/s12954-020-00393-0 ER - TY - JOUR T1 - Awareness of users and motivational factors for using new psychoactive substances in Belgium. JF - Harm Reduct J Y1 - 2020 A1 - Sarah Simonis A1 - Michael Canfyn A1 - Anton Van Dijck A1 - Tina Van Havere A1 - Eric Deconinck A1 - Peter Blanckaert A1 - L. Gremeaux KW - illicit drugs KW - new psychoactive substances KW - Substance use AB -

BACKGROUND: Few data on motivations for using new psychoactive substances (NPS) are available. However, the cost, the legal status, and their accessibility through channels like internet contributed to the popularity of NPS. The objective of this article are first to gain a deeper understanding of the culture surrounding NPS in Belgium and second to define the awareness of the users concerning the content of the NPS they are consuming.

METHODS: Snowball sampling and partners in the drug demand reduction field were used as a gateway in order to reach a heterogeneous study population. In total, 45 users were recruited and in-depth interviews were conducted. The personal experiences of NPS users and their needs for support along the continuum of care were explored through an interview guideline, while subjects were given the opportunity to deposit a NPS sample for forensic analysis in a recognized laboratory.

RESULTS: A diversity of profiles was found among NPS users but also a wide diversity in the motives to consume NPS: personal reasons such as pleasure, mind exploration, being connected to others, or out of curiosity, but also external reasons such as price, accessibility or the specific effects procured by certain NPS. The results showed as well that a majority of NPS users seem to be aware of the substances they are using.

CONCLUSION: Understanding the motivations of use is of importance to determine which type of NPS targeted interventions are adapted to different profiles of users.

VL - 17 CP - 1 M3 - 10.1186/s12954-020-00393-0 ER - TY - THES T1 - Chemical and toxciological characterization of e-liquid cigarettes Y1 - 2020 A1 - Sophia Barhdadi A1 - Eric Deconinck KW - E-sigaret AB -

The popularity of the electronic cigarette (e-cigarette) has increased significantly in the past decade. In Belgium, the implementation of the revised European Tobacco Products Directive (TPD) in 2014 marked a turning point for this phenomenon. Prior to this, the use of the e-cigarette was not yet mainstream, as only nicotine-free e-cigarettes were allowed on the market. However, as a result of the legislative changes, nicotine-containing e-cigarettes became freely available on the market and ‘vapeshops’ skyrocketed since then. As the number of e-cigarette users increased, so did the media coverage about the benefits and dangers of the e-cigarette, whether scientifically substantiated or not. To assure public health, scientific research about the safety and quality of the e-cigarette is of great importance. The objective of this PhD thesis was therefore to first determine the chemical composition of the liquids used in e-cigarettes (e-liquid) and next to investigate toxicological aspects of flavouring substances present in e-liquid refills.

First, a comprehensive literature search was performed to obtain an overview about the chemical composition of the e-liquids and the analytical methods used for their detection. Although the analytical methods used in these studies have not always been well validated and thus the results of these studies need to be critically examined; three main problems could be uncovered: (1) the content of nicotine in the e-liquids often does not correspond to the claimed concentration, (2) there is a significant presence of hazardous impurities and contaminants in the e-liquids and (3) food flavourings (diacetyl and acetylpropionyl) which are toxic when inhaled are also present.

In order to analyse the composition of the e-cigarettes and to check the e-liquids for the abovementioned issues, alternative methods were developed for the quantitative determination of nicotine and its related impurities (HPLC-DAD) and for the flavours diacetyl and acetylpropionyl (HS/GC-MS). Also, screening methods were developed for the identification of volatile organic compounds (HS/GC-MS) and the additives taurine (LC-MS/MS) and caffeine (GC-MS). Subsequently, the influence of the revised TPD on the quality of e-liquids available on the Belgian market was investigated using these developed methods. A total of 246 e-liquids were purchased before (2013-2016), during (2016) and after (2017-2018) the implementation of the revised TPD. The samples were examined for the presence of nicotine, nicotine-related impurities, volatile organic compounds, caffeine, taurine and the harmful flavours diacetyl and acetylpropionyl. In general, the legislative changes have had a positive effect on the quality of e-liquids: the results of our study show that the quality of e-liquids has improved following the implementation of the revised TPD. Indeed, in recent years, there have been significantly fewer discrepancies between the effective nicotine content and the claimed concentration. No hazardous volatile organic compounds were found in the 2017-2018 samples compared to the samples before the TPD. In 2018, 5% of the samples contained caffeine, compared to 16% in 2017. The food flavours diacetyl and acetylpropionyl were still present in e-liquids with a sweet, buttery taste such as cake, caramel, popcorn (55% in 2017 compared to 27% in 2018).

Next, as a test case, the risk of inhaling diacetyl present in e-liquids was investigated. An adapted risk assessment methodology for intentional inhalation of substances through the e-cigarette was applied. This exercise showed that there is no risk for systemic toxicity related to diacetyl vapours. However, the risk for local lung toxicity (lung tissue lesions associated with chronic pulmonary bronchiolitis obliterans) could not be excluded in case of repeated exposure to diacetyl through e-cigarette use.

In the final experimental part of the thesis, we focused on the identification of potential genotoxic flavouring substances in e-liquids through the use of non-animal methodologies. As such, 807 flavouring substances were identified in 129 e-liquids using complementary HS-GC MS methods. In a first step, all these substances were screened for genotoxicity using qualitative and quantitative in silico models. In total, potential genotoxicity activity was predicted for 44 flavourings. Based on information from European databases, genotoxicity could be confirmed for five of these flavourings (estragole, safrole, 2-furylmethylketone, 2,5-dimethyl-4-hydroxyl-3(2H)-furanone and transhexanal). Genotoxicity could be excluded for 23 flavourings. For the remaining 16 flavourings, insufficient information on their genotoxicity was present. For four of these flavourings, a commercial standard was available and thus could be tested in vitro using an Ames- and micronucleus test. One of the four substances was only slightly positive in the micronucleus test (b-hellandrene), while for isoledene, 2,3-butanedione and 2,3-pentanedione a clear positive result was obtained in at least one of the two in vitro tests.

Finally, in order to minimise potential health risks imposed by the use of e-cigarettes, some recommendations are suggested to further amend the current e-cigarette legislation.

PB - Vrije Universiteit Brussel (VUB) CY - Brussels, Belgium ER - TY - JOUR T1 - Discrimination of legal and illegal Cannabis spp. according to JF - Drug testing and analysis Y1 - 2020 A1 - Céline Duchateau A1 - Kauffmann, Jean-Michel A1 - Michael Canfyn A1 - Stévigny, Caroline A1 - De Braekeleer, Kris A1 - Eric Deconinck AB -

Aerial parts containing cannabidiol can be purchased in a legal way but cannabis used

as recreational drug is illegal in most European countries. Δ9-tetrahydrocannabinol is

one of the main cannabinoids responsible for the psychotropic effect. European

Union countries and Switzerland authorize a concentration of THC of 0.2 % and 1.0

% w/w, respectively, for smoking products and industrial hemp. Public health inspectors

and law enforcement officers need to check the legality of samples. Therefore

there is a need for innovative approaches, allowing quality control of these products

in an easy way and preferably on site. In many countries, cultivation of industrial

hemp is permitted if the THC content does not exceed 0.2 % w/w. A portable equipment

could be a useful measuring tool for farmers to check for the THC content at

regular time. In this work, 189 samples were analysed with a benchtop and a handheld

NIR device in order to create two classification methods according to European

and Swiss laws. All samples were also analysed by GC-FID to determine their THC

concentration. Supervised analysis was applied in order to establish the best model.

For the first classification, the accuracy was 91% for the test set with the benchtop

data and 93 % for the test set with the handheld data. For the second classification,

the accuracies were respectively 91 % and 95 %. The obtained models, hyphenating

spectroscopic techniques and chemometrics, enable to discriminate legal and illegal

cannabis samples according to European and Swiss laws.

CP - 12 M3 - 10.1002/dta2865 ER - TY - Generic T1 - Involvement of the Belgian OMCL in the COVID-19 crisis Y1 - 2020 A1 - Eric Deconinck JF - OMCL annual meeting General Session PB - EDQM CY - tele conference CP - EDQM ER - TY - Generic T1 - MSSFP004 Sildenafil: Chemometric Analysis Y1 - 2020 A1 - Eric Deconinck A1 - Mariangela Raimondo JF - API-WG CP - EDQM ER - TY - Generic T1 - MSSIP005: Products containing “non-INN” APIs Y1 - 2020 A1 - Eric Deconinck A1 - Marie Bertrand JF - Illegal Medicines Working Group EDQM PB - EDQM CY - Tele conference CP - EDQM ER - TY - JOUR T1 - The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind. JF - Drug Test Anal Y1 - 2020 A1 - Celine Vanhee A1 - Antoine Francotte A1 - Steven Janvier A1 - Eric Deconinck AB -

At the end of 2017 and 2018 two different unknown suspicious preparations were encountered and were subjected to a plethora of different analyses in order to identify, if present, any bioactive compound. It turned out that these samples contained the assumedly cognitive enhancing research peptides Selank and Semax, which, to our knowledge, have not completed any clinical trials. Moreover, an online search, excluding the dark web, demonstrated that these kinds of nootropic research peptides are freely available either as lyophilized powder for injection purposes or are present in nasal sprays. It stands to reason that controlling laboratories need to anticipate the uprising of these types of potentially dangerous molecules and must therefore be able to correctly identify these compounds. Therefore, these findings served as an incentive to develop a novel combined liquid chromatography tandem mass spectroscopy (LC-MS/MS) methodology, applicable to both hydrophilic or more hydrophobic peptides, which was utilized to analyze a total of 10 putative cognitive enhancing polypeptides, with variable biochemical characteristics, that are currently being sold online. The screening rationale, complying to the recommendation paper of the General European Official Medicines Control Laboratory (OMCL) network on the interpretation of screening results for unknown peptides by mass spectrometry, was also validated in different matrices as required by ISO 17025.

VL - 12 CP - 3 M3 - 10.1002/dta.2717 ER - TY - JOUR T1 - Report on a New Opioid NPS: Chemical and In Vitro Functional Characterization of a Structural Isomer of the MT-45 Derivative DiphenpipenolAbstract JF - Journal of Analytical Toxicology Y1 - 2020 A1 - Annelies Cannaert A1 - Fabian Hulpia A1 - Martijn Risseeuw A1 - Katleen Van Uytfanghe A1 - Eric Deconinck A1 - Van Calenbergh, Serge A1 - Peter Blanckaert A1 - Stove, Christophe M3 - 10.1093/jat/bkaa066 ER - TY - JOUR T1 - Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene JF - Drug Testing and Analysis Y1 - 2020 A1 - Peter Blanckaert ED - Annelies Cannaert ED - Katleen Van Uytfanghe ED - Fabian Hulpia ED - Eric Deconinck ED - Van Calenbergh, Serge ED - Stove, Christophe VL - 12 CP - 4 M3 - 10.1002/dta.2738 ER - TY - JOUR T1 - Sensitizing fragrances in absorbent hygiene products. JF - Contact Dermatitis Y1 - 2020 A1 - Bart Desmedt A1 - Quinten Marcelis A1 - Dea Zhilivoda A1 - Eric Deconinck AB -

BACKGROUND: Allergenic fragrances are present in a wide range of products but they are not regulated in all industries to the same extent. In Europe, absorbent hygiene products (AHP's) are only covered by the general product safety directive and therefore fragrances can be used freely, while in cosmetics and toys the use of these ingredients is regulated.

METHOD: An analytical method was developed to evaluate the presence of 24 sensitizing fragrances in AHP's. This method allows simultaneous identification and quantification and was validated using the total error approach with an acceptance value of ±15%.

RESULTS: The validated method was applied to evaluate 10 scented AHPs consisting of four tampons, three panty liners, and three sanitary pads. Eight allergenic fragrances were identified in these products and five products contained at least one allergen above 10 μg/g.

CONCLUSION: The presence of these allergens is not communicated to the consumer. This is, however, a strict requirement in other industries (e.g. cosmetics, toys) to ensure adequate consumer protection. Knowing that the exposed area is more susceptible to allergens and irritants, the presence of these allergens should be disclosed. This article is protected by copyright. All rights reserved.

M3 - 10.1111/cod.13472 ER - TY - JOUR T1 - Substandard and falsified antimicrobials: A potential biohazard in disguise? JF - Drug Testing and Analysis Y1 - 2020 A1 - Yaxin Tie A1 - Erwin Adams A1 - Eric Deconinck A1 - Celine Vanhee M3 - 10.1002/dta.2740 ER - TY - JOUR T1 - Substandard and falsified antimicrobials: A potential biohazard in disguise? JF - Drug Test Anal Y1 - 2020 A1 - Yaxin Tie A1 - Erwin Adams A1 - Eric Deconinck A1 - Celine Vanhee VL - 12 CP - 2 M3 - 10.1002/dta.2740 ER - TY - Generic T1 - Allergenic fragrances in absorbent hygiene products Y1 - 2019 A1 - Bart Desmedt A1 - Quinten Marcelis A1 - Dea Zhilivoda A1 - Eric Deconinck PB - E&L conference CY - London ER - TY - Generic T1 - API Testing: how OMCLs can support the control of APIs Y1 - 2019 A1 - Eric Deconinck A1 - Yvan Grange JF - EDQM and European Pharmacopoeia: State-of-the-art Science for Tomorrow’s Medicines PB - EDQM CY - Strasbourg, France ER - TY - RPRT T1 - Benefits of Chemometrics for OMCLs Y1 - 2019 A1 - Eric Deconinck A1 - Jelena Acevska A1 - Hervé Ribière PB - EDQM CY - Strasbourg, France ER - TY - Generic T1 - Characterization and hazard identification of substandard and falsified antimicrobials encountered in Belgium Y1 - 2019 A1 - Yaxin Tie A1 - Celine Vanhee A1 - Eric Deconinck A1 - Erwin Adams AB -

Antimicrobials are, together with anti-malarials, one of the most popular medicines that have been encountered as illegal substandard and falsified (SF) medical products. It has been demonstrated that SF products of these essential life-saving medicines could cause treatment failures, antimicrobial resistance and drug side effects [1]. Therefore, validated and robust analytical tools enabling the identification and quantification of active pharmaceutical ingredients (APIs) potentially present in these suspicious SF antimicrobials, are paramount. Here, a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS2) screening method is presented, taking only 15 minutes, for the identification of 36 different antimicrobials and 1 beta-lactamase inhibitor. Furthermore, upon identification, a subsequent quantification method using ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD) was also successfully validated. Next, real-life illegal antimicrobial samples, confiscated by inspectors from the Belgium Federal Agency for Medicines and Health Products (FAMHP), were subjected to our identification and quantification methodology. The obtained data indicated that about half of the samples were underdosed, resulting in a potential lower efficacy and so may aggravate illness of patients and induce bacterial resistance [2].

Moreover, in order to have an in-depth characterization of SF-antimicrobials, collected samples were also evaluated in terms of impurities and dissolution. The impurities were analyzed based on the methods of the European Pharmacopoeia (Ph. Eur.) and the dissolution methods were adopted from the United States Pharmacopeia (USP) [3-4]. Moreover, the dissolution profiles of SF antimicrobials were compared to the ones of their genuine counterparts. In general, about 35% of the samples contained known and/or unknown impurities beyond the Ph. Eur. limits [3]. Concerning the dissolution tests, 47% of samples were not compliant as the amount of drug released is under the limit at the time point described by the USP [4].

Taken together, the above-mentioned results demonstrate that these in Belgium encountered SF antimicrobials, could pose a serious threat to public health due to underdosing, presence of impurities or improper dissolution. The low quality of these products could result in treatment failure and induction of bacterial resistance.

JF - RDPA CY - Pescara, Italy ER - TY - JOUR T1 - Combining Attenuated Total Reflectance- Infrared Spectroscopy and chemometrics for the identification and the dosage estimation of MDMA tablets JF - talanta Y1 - 2019 A1 - Eric Deconinck A1 - Raf Van Campenhout A1 - Cherazade Aoudi A1 - Michael Canfyn A1 - Bothy, Jean-Luc A1 - Peter Blanckaert A1 - L. Gremeaux A1 - Patricia Courselle KW - ATR-(N)IR KW - Chemometrics KW - illicit drugs KW - Mobile detection approaches VL - 195 M3 - ://doi.org/10.1016/j.talanta.2018.11.027 ER - TY - Generic T1 - Comparative dissolution study on substandard and falsified antibiotics encountered in Belgium Y1 - 2019 A1 - Yaxin Tie A1 - Kevin van Loock A1 - Erwin Adams A1 - Eric Deconinck AB -

Antimicrobials are, together with anti-malarials, the most popular medicines that have been encountered as illegal substandard and falsified (SF) medical products. SF antimicrobials are gaining popularity both in developing and developed countries, posing a growing threat to public health. It has been demonstrated that SF products of these essential life-saving medicines could cause treatment failures, antimicrobial resistance and drug side effects [1]. In general, the evaluation of SF antimicrobials mainly focuses on the identification and quantification of the active pharmaceutical ingredients (APIs), ignoring other parameters of drug quality control [2]. In this context, SF antimicrobials containing the correct dosage of claimed APIs can exhibit poor dissolution performance. Thus, it is necessary and crucial to execute in vitro dissolution studies on SF antimicrobials to estimate the in vivo bioavailability and bioequivalence.

Real-life illegal antimicrobial samples, confiscated by inspectors from the Belgium Federal Agency for Medicines and Health Products (FAMHP), were subjected to dissolution studies. The results indicated that 9 out of 19 illegal samples failed to meet the dissolution limits prescribed by the United States Pharmacopeia. The dissolution profiles of illegal SF antimicrobials were mathematically compared to their genuine counterparts using f1 and f2-methods, which clearly demonstrate low equivalences of dissolution profiles between SF antimicrobials and genuine products. The potential low drug efficacy induced by improper dissolution of SF antimicrobials could aggravate illness and even promote antimicrobial resistance.

JF - ULLA Summer School CY - Helsinki, Finland ER - TY - THES T1 - Comparative Study between dissolution profiles of genuine and falsified antibiotics Y1 - 2019 A1 - Kevin Van Loock A1 - Y. Vander Heyden A1 - Yaxin Tie A1 - Eric Deconinck KW - Counterfeit antimicrobials PB - VUB CY - Jette ER - TY - JOUR T1 - Consumer protection provided by the European medical device and cosmetic legislation for condoms and lubricants. JF - Regul Toxicol Pharmacol Y1 - 2019 A1 - Bart Desmedt A1 - M Vanhamme A1 - Celine Vanhee A1 - Rogiers, V A1 - Eric Deconinck KW - Condoms KW - Consumer Product Safety KW - Cosmetics KW - European Union KW - Humans KW - Lubricants KW - Risk Assessment AB -

Personal lubricants and lubricants used in condoms contain a number of ingredients which are also present in cosmetic products. These have to comply to the medical device regulation (745/2017) which should provide the same level of consumer protection, if not more, as foreseen in the legal framework of cosmetics (1223/2009). In the current study we developed an analytical method capable of identifying and quantifying 15 ingredients, commonly found in lubricants and cosmetics. Based upon their most important toxicological endpoint, the substances involved were grouped in three toxicological classes provoking either irritation, contact allergic dermatitis or systemic toxicity. The method was applied on 30 condoms and 54 personal lubricants present on the EU market. Their safety was assessed using the same reasoning as commonly applied for cosmetic ingredients. Higher mucosae susceptibility, the main exposed area for lubricants, was taken into account in this assessment. The results show that the majority of the products studied are safe. Nevertheless, for some products the safety could not be confirmed. The results also highlight the fact that there is no consensus for a number of ingredients, used as well in cosmetics as in medical devices. Alignment between both legislations would improve the safety of these products and further raise the general level of consumer protection.

VL - 103 M3 - 10.1016/j.yrtph.2019.01.022 ER - TY - JOUR T1 - Development and validation of chromatographic methods for screening and subsequent quantification of suspected illegal antimicrobial drugs encountered on the Belgian market. JF - Talanta Y1 - 2019 A1 - Yaxin Tie A1 - Celine Vanhee A1 - Eric Deconinck A1 - Erwin Adams AB -

Estimations, made by the World Health Organization (WHO), state that 10% of the medical products in low- and middle-income countries are substandard or falsified (SF). Among them, antibiotics and antimalarials are the most commonly reported since 2013. Besides the fact that falsification is a crime, the worldwide use of poor quality antimicrobials could result in treatment failures, stronger antimicrobial resistance and even the promotion of the emergence of superbugs. Therefore, simple and accurate analytical methods are necessary, which are capable to detect and quantify a wide range of antimicrobials in suspected illegal products. In this work, a screening and a quantification method using ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS) and diode array detection (UHPLC-DAD), respectively were developed and validated. These methods could be used for routine analysis and enable a more in-depth characterization of SF-antimicrobials. According to their popularity as SF-antimicrobials, 31 antibiotics, 3 antibacterial agents, 1 antifungal agent and 1 beta-lactamase inhibitor, covering eleven different antibacterial classes, were selected. The UHPLC-MS screening method with gradient elution is able to selectively detect these 36 compounds within 18 min (including wash and equilibration step). It was validated for sensitivity, selectivity and matrix effects. Within an analysis time of 32 min, the UHPLC-DAD method could quantify 32 compounds (4 showed insufficient UV absorbance) and resulted in sufficient selectivity, necessary since some SF-antimicrobials may include more than one antimicrobial component. This quantification method was validated for the positive hits found during screening tests of suspected illegal samples. This resulted in a validation set of 11 antimicrobials and 1 beta-lactamase inhibitor. The ''total error'' approach in accordance with the validation requirements of ISO-17025 was employed for the validation. 57 real-life illegal samples, seized by inspectors from the Belgium Federal Agency for Medicinal and Health Products (FAMHP), were analyzed using the two described methods. About half of them were not compliant and some samples that contained clavulanic acid showed a serious reduction in the amount of this molecule (in one sample only 14% of the claimed dosage was found). These quality issues might be attributed to either poor manufacturing, storage or transportation conditions.

VL - 194 M3 - 10.1016/j.talanta.2018.10.078 ER - TY - JOUR T1 - Development and validation of chromatographic methods for screening and subsequent quantification of suspected illegal antimicrobial drugs encountered on the Belgian market JF - Talanta Y1 - 2019 A1 - Yaxin Tie A1 - Celine Vanhee A1 - Eric Deconinck A1 - Erwin Adams KW - Substandard and falsified antimicrobials KW - UHPLC-DAD KW - UHPLC-MS2 AB -

Estimations, made by the World Health Organization (WHO), state that 10% of the medical products in low- and middle-income countries are substandard or falsified (SF). Among them, antibiotics and antimalarials are the most commonly reported since 2013. Besides the fact that falsification is a crime, the worldwide use of poor quality antimicrobials could result in treatment failures, stronger antimicrobial resistance and even the promotion of the emergence of superbugs. Therefore, simple and accurate analytical methods are necessary, which are capable to detect and quantify a wide range of antimicrobials in suspected illegal products. In this work, a screening and a quantification method using ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS2) and diode array detection (UHPLC-DAD), respectively were developed and validated. These methods could be used for routine analysis and enable a more in-depth characterization of SF-antimicrobials.

According to their popularity as SF-antimicrobials, 31 antibiotics, 3 antibacterial agents, 1 antifungal agent and 1 beta-lactamase inhibitor, covering eleven different antibacterial classes, were selected. The UHPLC-MS2 screening method with gradient elution is able to selectively detect these 36 compounds within 18 min (including wash and equilibration step). It was validated for sensitivity, selectivity and matrix effects. Within an analysis time of 32 min, the UHPLC-DAD method could quantify 32 compounds (4 showed insufficient UV absorbance) and resulted in sufficient selectivity, necessary since some SF-antimicrobials may include more than one antimicrobial component. This quantification method was validated for the positive hits found during screening tests of suspected illegal samples. This resulted in a validation set of 11 antimicrobials and 1 beta-lactamase inhibitor. The ''total error'' approach in accordance with the validation requirements of ISO-17025 was employed for the validation. 57 real-life illegal samples, seized by inspectors from the Belgium Federal Agency for Medicinal and Health Products (FAMHP), were analyzed using the two described methods. About half of them were not compliant and some samples that contained clavulanic acid showed a serious reduction in the amount of this molecule (in one sample only 14% of the claimed dosage was found). These quality issues might be attributed to either poor manufacturing, storage or transportation conditions.

VL - 194 M3 - 10.1016/j.talanta.2018.10.078 ER - TY - THES T1 - The development of a characterisation approach for Amphetamine, Cocaine and Ketamine samples, using infrared and Raman techniques Y1 - 2019 A1 - Andries Raes A1 - Tamara Vanhaecke A1 - Eric Deconinck PB - VUB CY - Jette ER - TY - Generic T1 - Development of a sample preparation method for the GC-analysis of e-cigarette refill liquids Y1 - 2019 A1 - Sophia Barhdadi A1 - Michael Canfyn A1 - Bart Desmedt A1 - Sanae El Merabety A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Tamara Vanhaecke A1 - Eric Deconinck AB -

Since its introduction more than 10 years ago, the e-cigarette has become a commonly used consumer product. To guarantee the users safety, analytical characterization of the refill liquids (e-liquids) used for e-cigarettes is essential. Different techniques have been used for the qualitative and quantitative chemical characterization of e-liquids of which gas-chromatography is the most often used technique as e-liquids mainly consist out of (semi)-volatile ingredients (i.e. nicotine and flavourings) dissolved in a propylene glycol and glycerol matrix. The e-liquid matrix is viscous and greasy which may result in a faster deterioration of the GC-columns and deactivate the interaction with the active groups. To overcome this issue, a proper sample preparation is needed, to improve the life span of the column and reduce the total number of cuts in the GC-column.

The aim of our study is to quantify potential harmful flavourings used in e-cigarettes using GC-method with an appropriate sample preparation. The group of flavourings are divided in two groups: high and low semi-volatiles. High volatile flavouring group contains the flavourings diacetyl and acetylpropionyl. The low and semi-volatiles contain potential genotoxic flavourings, selected through in-silico genotoxicity screening of 436 identified components in 77 e-liquid samples. These components are pulegone, estragole, 5-methylfurfural, 2-furylmethylketon, methylnaphthalene, trans-menthone and trans-2-hexanal.

For the high volatiles flavourings headspace is considered to limit the transfer of the matrix to the column. The headspace temperature was chosen in  order to obtain an optimal transfer of the target components to the headspace with minimal transfer of the matrix components. The e-liquid was dissolved in water, to shift the equilibrium of the target components towards the headspace and to enhance the retention of the matrix components. The optimal headspace temperature was set at 85°. For the low and semi volatiles, full evaporation conditions (145°C) of the headspace were considered. In this case a sample clean-up is needed to avoid transfer of the matrix components to the column. Different sample clean up techniques were tested. Finally the liquid-liquid extraction (LLE) with freeze out using flash cooling technique was optimized. This sample preparation techniques can also be used with other GC-injection techniques. Both methodologies were further optimized and validated for quantification of the target components using matrix-matched calibration

The sample preparation of most quantification methods for e-liquids only consisted of simple dilute and shoot methodologies. In this study, we successfully developed a clean-up technique to eliminate most of the matrix components. The sample preparation of LLE with freeze out using flash cooling technique is a sample preparation which could be applied and optimized for other target components in e-liquids.

JF - Euroanalysis XX - 1-5 September 2019, Istanbul ER - TY - JOUR T1 - Evaluation of impurities and dissolution profiles of illegal antimicrobial drugs encountered in Belgium JF - Drug testing and analysis Y1 - 2019 A1 - Yaxin Tie A1 - Kevin van Loock A1 - Eric Deconinck A1 - Erwin Adams M3 - https://doi.org/10.1002/dta.2690 ER - TY - RPRT T1 - Example 6: Falsified/Illegally APIs to the position paper “An aide mémoire for the Testing of Suspected Illegally Traded and Falsified Medicines”, PA/PH/OMCL (06) 81 R10 Y1 - 2019 A1 - Eric Deconinck A1 - Yvan Grange PB - EDQM CY - Strasbourg, France ER - TY - Generic T1 - Impact of the revised European Tobacco Product Directive on the quality of e-cigarette refill liquids in Belgium Y1 - 2019 A1 - Sophia Barhdadi A1 - Moens, Goedele A1 - Michael Canfyn A1 - Celine Vanhee A1 - Bart Desmedt A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Vanhaecke, Tamara A1 - Eric Deconinck KW - e-cigarettes AB -

Introduction: Since its introduction more than 10 years ago, the e-cigarette has become a commonly used consumer product. This success has led in 2014 to the revision of the European Tobacco Product Directive (TPD) which came to force by the end of 2016, since then also containing mandatory rules to assure the quality and safety of electronic nicotine delivery systems. In this study, we investigate whether these regulatory changes had an impact on the quality of refill liquids (e-liquids) available on the Belgian market through analysis of their chemical composition.

 

Methods: By using in-house validated methods, a total of 246 e-liquids purchased prior (2013-2015), during (2016) and after (2017-2018) the implementation of the TPD revisions, were analyzed for the presence of nicotine, nicotine-related impurities, volatile organic compounds (VOCs), the additives caffeine and taurine, and the flavours diacetyl and acetylpropionyl.

 

Results: Although not all manufacturers manage to produce and label their products accurately, nicotine labelling discrepancies have decreased over time. Before the revised TPD came into force, almost half of the samples was not conform in contrast to less than 15% non-conformities observed in the period 2017-2018. Moreover, also the number of e-liquids, containing high risk VOCs (10% in 2016 versus none of the samples in 2017-2018), caffeine (16% in 2017 versus 5% in 2018) and diacetyl and acetylpropionyl (55% in 2017 versus 27% in 2018 of sweet flavoured samples) diminished over time.

 

Conclusion: Our results demonstrate that the overall quality of the e-liquids has improved after the implementation of the revised TPD. However, the results also show that periodic quality control might be required to ensure further compliance to the TPD.

 

Implications: This study clearly demonstrates that the implementation of the revised TPD has improved the quality of the e-liquids on the Belgian market. However, there are still e-liquids that are not in agreement with the TPD due to nicotine concentration label discrepancies, presence of e-liquid impurities and of the controversial flavours diacetyl and acetylpropionyl or the additive caffeine.

JF - 20th Forum of Pharmaceutical Sciences - Brussels - 20 May 2019 ER - TY - JOUR T1 - Lessons to be learned from toxicological analyses in intoxicated patients and seized materials at an electronic music dance festival JF - Forensic Science International Y1 - 2019 A1 - Paul Calle A1 - Kristof Maudens A1 - Sabine Lemoyne A1 - Simon Geerts A1 - Diederik Van Sassenbroeck A1 - Peter Jensen A1 - Jorne Van Overloop A1 - Eric Deconinck A1 - Peter Blanckaert VL - 299 M3 - 10.1016/j.forsciint.2019.03.047 ER - TY - Generic T1 - MSSFP004 on Sildenafil – Status report and repartition of test parameters Y1 - 2019 A1 - Eric Deconinck A1 - Maria Joao Portella A1 - Marie Bertrand JF - EDQM API-working group PB - EDQM CY - Strasbourg, France CP - EDQM ER - TY - Generic T1 - MSSIP005: Products containing “non-INN” APIs Y1 - 2019 A1 - Eric Deconinck A1 - Marie Bertrand JF - EDQM Illegal medicines Working Group CY - Warsaw, Poland CP - EDQM ER - TY - Generic T1 - MSSIP005 – Status of combined pro- and retrospective market surveillance study with focus on designer molecules in dietary supplements (excluding INN drugs) Y1 - 2019 A1 - Eric Deconinck A1 - Marie Bertrand JF - EDQM Illegale Medicine Working Group PB - EDQM CY - London, UK CP - EDQM ER - TY - JOUR T1 - Report on a novel emerging class of highly potent benzimidazole NPS opioids: chemical and in vitro functional characterization of isotonitazene JF - Drug Testing and Analysis Y1 - 2019 A1 - Peter Blanckaert A1 - Annelies Cannaert A1 - Katleen Van Uytfanghe A1 - Fabian Hulpia A1 - Eric Deconinck A1 - Van Calenbergh, Serge A1 - Stove, Christophe M3 - 10.1002/dta.2738 ER - TY - BOOK T1 - Residual solvents in pharmaceutical substances and products T2 - Residual solvents in pharmaceutical substances and products Y1 - 2019 A1 - Eric Deconinck A1 - Bart Desmedt JF - Residual solvents in pharmaceutical substances and products PB - Elsevier CY - Toronto, Canada VL - 2 CP - 1201 ER - TY - JOUR T1 - The role of liquid chromatography and gas chromatography in the analysis of illegal medicines and health products JF - LC-GC Europe Y1 - 2019 A1 - Yaxin Tie A1 - Celine Vanhee A1 - Erwin Adams A1 - Eric Deconinck VL - 32 CP - 2 ER - TY - JOUR T1 - A simple dilute-and-shoot method for screening and simultaneous quantification of nicotine and alkaloid impurities in electronic cigarette refills (e-liquids) by UHPLC-DAD JF - Journal of Pharmaceutical and Biomedical Analysis Y1 - 2019 A1 - Sophia Barhdadi A1 - Bart Desmedt A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Vanhaecke, Tamara A1 - Eric Deconinck KW - accuracy profiles KW - e-cigarettes KW - Nicotine KW - nicotine-impurities KW - UHPLC-DAD AB -

The electronic cigarette (e-cigarette) has emerged as a popular alternative to the traditional hazardous tobacco cigarette. The substantial increase in e-cigarette use also urgently calls for controlling the quality of e-cigarette refill liquid products (e-liquids). Currently, the most important quality indicator of e-liquid products is the quantification of nicotine and its related impurities. Although different methods have been published to measure nicotine and impurity levels, the majority of them use a targeted LC-MS/MS approach. There is, however, a need for more robust quantification methods that are easy to implement in most control (industrial and governmental) laboratories. Therefore, in this study, a simple dilute-and-shoot UHPLC-DAD method has been developed and validated for the simultaneous quantification of nicotine and its alkaloid impurities in electronic cigarette refills. An optimal separation of the alkaloids was achieved in a runtime of 11 min. The method was successfully validated using the “total error” approach in accordance with the validation requirements of ISO-17025. During this validation, interference between the target components and a number of popular flavouring compounds such as vanillin, maltol, ethylacetate, etc. could be excluded. In addition, small changes to the column temperature, pH and molar concentration of the mobile phase buffer were deliberately introduced in order to assess the robustness of the method. Only a slightly different outcome between the newly developed UV-detection method and the targeted MS approach was found, due to the sensitivity of the different detection techniques. However, in the context of quality control of nicotine related impurities, for which the European Pharmacopoeia limits are currently applied, the sensitivity of the UHPLC-DAD method was found to be within the acceptable range. Despite the somewhat lower selectivity of the newly developed UV-detection technique versus a targeted LC-MS/MS approach, it may be concluded that this method is a suitable alternative for quality control purposes.

VL - 169 CP - 169 M3 - 10.1016/j.jpba.2019.03.002 ER - TY - JOUR T1 - A strategy based on fingerprinting and chemometrics for the detection of regulated plants in plant food supplements from the Belgian market: two case studies JF - journal of pharmaceutical and biomedical analysis Y1 - 2019 A1 - Eric Deconinck A1 - Melissa Van Hamme A1 - Bothy, Jean-Luc A1 - Patricia Courselle AB -

The sale and consumption of plant food supplements is increasing, especially in the western world. A lot of these supplements can be bought through internet, where a lot of illegal trade is going on. Every year seized dietary supplements are send to laboratories in order to screen for the presence of chemical adulterants or illegally added active pharmaceutical ingredients, though also herbal adulteration occurs and is given less attention.

In this paper a two-step approach is presented based on fingerprints recorded by both infrared spectroscopy as liquid chromatography with UV-detection for the screening of five regulated plants used in respectively dietary supplements for slimming and potency enhancement. Both types of fingerprints are combined with chemometric techniques in order to obtain classification models. A first classification model is calculated based on the infrared data and gives a first idea about the plant suspected to be present. This suspicion is then confirmed based on binary classification models calculated with the chromatographic data obtained for the suspected plant. In general, good classification models were obtained for each of the targeted plants.

The approach was applied in a small market study comprising 35 dietary supplements for slimming and 34 for male potency enhancement. In total 21 samples were found to contain one of the five targeted plants.

VL - 166 ER - TY - JOUR T1 - Trends in the analysis of falsified and illegal medicines JF - Talanta Y1 - 2019 A1 - Eric Deconinck VL - 203 M3 - https://doi.org/10.1016/j.talanta.2019.05.074 ER - TY - Generic T1 - Activities in NPS & Data Sharing Y1 - 2018 A1 - Eric Deconinck JF - CLEN meeting WG Data Sharing PB - JRC CY - Brussels, Belgium CP - DG TAXUD European Commission and JRC ER - TY - Generic T1 - API-WG Project: chemometric results for omeprazole Y1 - 2018 A1 - Eric Deconinck KW - API fingerprinting JF - API-WG PB - EDQM CY - Strasbourg CP - EDQM ER - TY - Generic T1 - ATYPICAL MARKET SURVEILLANCE STUDY ON OMEPRAZOLE API’S, CHEMOMETRIC RESULTS FOR OMEPRAZOLE Y1 - 2018 A1 - Eric Deconinck JF - Counterfeit WG meeting CP - EDQM ER - TY - Generic T1 - CAP 2017/18: instanyl 50 micrograms/dose nasal spray Y1 - 2018 A1 - Eric Deconinck A1 - Patricia Courselle JF - Annual CAP meeting CP - EDQM ER - TY - Generic T1 - Characterization of suspected illegal antimicriobials Y1 - 2018 A1 - Yaxin Tie A1 - Celine Vanhee A1 - Eric Deconinck A1 - Erwin Adams KW - API quantification KW - Impurity profiles JF - DA-PBA CY - Leuven, Belgium ER - TY - Generic T1 - Chemical characterization of electronic cigarette refills (e-liquids) in Belgium Y1 - 2018 A1 - Sophia Barhdadi A1 - Michael Canfyn A1 - Moens, Goedele A1 - Celine Vanhee A1 - Bart Desmedt A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Vanhaecke, Tamara A1 - Eric Deconinck KW - additives KW - e-cigarettes KW - GC KW - impurities KW - LC KW - Nicotine JF - 29th International Symposium on Pharmaceutical and Biomedical Analysis PB - Journal of Pharmaceutical and Biomedical Analysis CY - Leuven, Belgium ER - TY - Generic T1 - CLEN-Working Group “Data Sharing” Y1 - 2018 A1 - Eric Deconinck JF - Counterfeit WG EDQM PB - EDQM CY - Sarajevo, Bosnie-Herzegovina ER - TY - JOUR T1 - Detection and identification of multiple adulterants in plant food supplements using attenuated total reflectance—Infrared spectroscopy JF - Journal of Pharmaceutical and Biomedical Analysis Y1 - 2018 A1 - Eric Deconinck A1 - C. Aouadi A1 - Jean-Luc Bothy A1 - Patricia Courselle KW - ATR-(N)IR; Plant Food Supplements; Chemometrics; Mobile detection approaches VL - 152 M3 - 10.1016/j.jpba.2018.01.047 ER - TY - Generic T1 - Development and validation of a UHPLC-MS/MS screening method and a UHPLC-DAD quantification method for the analysis of counterfeit antimicrobials Y1 - 2018 A1 - Yaxin Tie A1 - Celine Vanhee A1 - Erwin Adams A1 - Eric Deconinck KW - accuracy profiles KW - Counterfeit antimicrobials KW - LC-DAD KW - LC-MS/MS JF - DA-PBA CY - Leuven, Belgium ER - TY - JOUR T1 - Falsification of biotechnology drugs: current dangers and/or future disasters? JF - J Pharm Biomed Anal Y1 - 2018 A1 - Steven Janvier A1 - De Spiegeleer, Bart A1 - Celine Vanhee A1 - Eric Deconinck KW - Biological Products KW - Counterfeit Drugs KW - Drug Contamination KW - Humans AB -

Falsified medical products have become a global threat since they were first mentioned to the general public at the conference of experts on the rational use of drugs organized by the world health organization (WHO) in 1985. Today, official estimates of the annual death toll due to falsified medical products range between two hundred thousand and one million. Although the extent of this global problem is the most significant in the developing world, an increasing number of reports have demonstrated the presence of a substantial (black) market for falsified medical products in the developed world. In recent years, also biotechnology drugs (synthetic peptide drugs and protein drugs) have been reported to be prone for falsifications. Next to the traditional doping related substances and image-enhancing polypeptides (e.g., human growth hormone, melanotan II) also essential medicines such as insulin, oxytocin and monoclonal antibodies have been falsified. The danger regarding the use of these falsified polypeptide drugs lies in the fact that end-users have no guarantee of the safety and efficacy of these preparations. Multiple reports have namely described the presence of the wrong active pharmaceutical ingredient (API), the wrong dosage or the absence of the API. Additionally, adverse health effects have been reported in the past due to toxic contaminations and product or process related impurities. Moreover, also unauthorized polypeptides or polypeptides which failed clinical trials or are still subject of clinical or pre-clinical assessments have been found in seizures of regulatory agencies. It stands to reason that regulatory agencies and analytical laboratories handling falsified biotechnology drugs have stepped up efforts to counter these grievous practices. The analysis of these falsified polypeptides and putative impurities is however not always straightforward. Often (bio)analytical laboratories have to resort to a combination of electrophoretic techniques, immunological assays and mass spectrometry based approaches to merely identify the content of seized samples. In addition, the difference in size (peptide vs proteins vs monoclonal antibodies), complexity (e.g., isoforms, glycosylations) and different synthesis techniques (chemical synthesis, recombinant expression, native protein isolation) result in a wide range of putative health risks. This review therefore aims to provide a brief overview of the genuine biotherapeutics present on the market and their quality prerequisites. Next, we describe the identification strategy utilised by our lab to identify the API in falsified biotherapeutics, followed by a discussion of the putative hazards due to impurities and contaminations that were found or could be encountered in falsified biotherapeutics. Finally, we terminate with an educational prediction of what may happen in the future and possible ways to counteract putative future disasters.

VL - 161 M3 - 10.1016/j.jpba.2018.08.037 ER - TY - JOUR T1 - Falsification of biotechnology drugs: current dangers and/or future disasters? JF - Journal of Pharmaceutical and Biomedical Analysis Y1 - 2018 A1 - Steven Janvier A1 - De Spiegeleer, Bart A1 - Celine Vanhee A1 - Eric Deconinck VL - 161 M3 - 10.1016/j.jpba.2018.08.037 ER - TY - Generic T1 - Falsified peptide medicines: poison or prejudice Y1 - 2018 A1 - Steven Janvier A1 - Celine Vanhee A1 - Bart de Spiegeleer A1 - Eric Deconinck JF - 29th International Symposium on Pharmaceutical and Biomedical Analysis CY - Leuven, Belgium ER - TY - JOUR T1 - Identification and Quantification Methodology for the Analysis of Suspected Illegal Dietary Supplements: Reference Standard or no Reference Standard, that the Question JF - Journal of Forensic Toxicology & Pharmacology Y1 - 2018 A1 - Celine Vanhee A1 - Emmy Tuenter A1 - Angelique Kamugisha A1 - Michael Canfyn A1 - Moens, Goedele A1 - Patricia Courselle A1 - Luc Pieters A1 - Eric Deconinck A1 - Vasiliki Exarchou VL - 07 CP - 01 M3 - 10.4172/2325-984110.4172/2325-9841.1000156 ER - TY - JOUR T1 - Identification of coffee leaves using FT-NIR spectroscopy and SIMCA. JF - Talanta Y1 - 2018 A1 - Mees, Corenthin A1 - Souard, Florence A1 - Delporte, Cedric A1 - Eric Deconinck A1 - Stoffelen, Piet A1 - Stévigny, Caroline A1 - Kauffmann, Jean-Michel A1 - De Braekeleer, Kris KW - Chemometrics KW - Coffee leaves KW - Fingerprints KW - FT-NIRS KW - SIMCA AB -

Abundant literature has been devoted to coffee beans (green or roasted) chemical description but relatively few studies have been devoted to coffee leaves. Given the fact that coffee leaves are used for food and medicinal consumption, it was of interest to develop a rapid screening method in order to identify coffee leaves taxa. Investigation by Fourier - Transform near infrared spectroscopy (FT-NIRS) was performed on nine Coffea taxa leaves harvested over one year in a tropical greenhouse of the Botanic Garden Meise (Belgium). The only process after leaves harvesting was an effective drying and a homogeneous leaves grinding. FT-NIRS with SIMCA analysis allowed to discriminate the spectral profiles across taxon, aging stage (mature and senescence coffee leaves) and harvest period. This study showed that it was possible (i) to classify the different taxa, (ii) to identify their aging stage and (iii) to identify the harvest period for the mature stage with a correct classification rate of 99%, 100% and 90%, respectively.

VL - 177 M3 - 10.1016/j.talanta.2017.09.056 ER - TY - Generic T1 - Identification of Flavouring Substances of Genotoxic Concern Present in E-Cigarette Refills Y1 - 2018 A1 - Sophia Barhdadi A1 - Birgit Mertens A1 - Melissa Van Bossuyt A1 - Michael Canfyn A1 - Patricia Courselle A1 - Rogiers, Vera A1 - Eric Deconinck A1 - Vanhaecke,T. KW - e-cigarettes KW - flavourings KW - genotoxicity AB -

Over the last years, the popularity of electronic e-cigarettes has increased significantly. An important contributor to this trend is the availability of a wide variety of flavours used in e-liquid refills. However, the role of these flavouring components in the potential toxicity of e-cigarette vapours remains unclear. Considering the large number of e-liquid flavours available on the market (> 7000), there is an urgent need to establish an efficient screening strategy to prioritize the substances of highest concern for human health. In this context, genotoxicity is a key (toxicological) endpoint as it is related to a broad range of adverse human health effects including cancer. Therefore, in this study, a prioritization strategy based on a combination of analytical screening, in silico prediction and literature consultation was developed for identifying potentially genotoxic substances in e-liquid flavours.

77 e-liquids, representative for the different flavour categories, were collected on the Belgian market and screened for their chemical composition using GC-MS. By using the National Institute of Standards and Technology (NIST) research library, 436 individual components could be identified. Next, the genotoxic potential of these individual components was investigated in silico with two complementary (quantitative) structure-activity relationship ((Q)SAR) models (Derek Nexus, Sarah Nexus). In total, 57 flavouring components were identified with a structural alert for genotoxicity in at least one of the two (Q)SAR models. For these substances, genotoxicity data was collected from previous European safety evaluations in different regulatory domains (e.g. by the European Chemical Agency (ECHA) and the European Food Safety Authority (EFSA)). Genotoxicity could be excluded for only 12 of the 57 components, whilst for 2 of them there is a clear concern for genotoxic potential. Data for the remaining components was missing or ambiguous and hence additional toxicological data is required in order to be able to exclude genotoxic potential.

The above findings indicate that the use of flavoring components might thus pose a potential health risk for e-cigarette users. Further research might explore to which extent these flavouring substances are transferred from the e-liquid into the e-cigarette vapours.

JF - EUROTOX 2018 PB - Toxicology Letters CY - Brussels, Belgium ER - TY - JOUR T1 - Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market JF - Talanta Y1 - 2018 A1 - Steven Janvier A1 - Karlien Cheyns A1 - Michael Canfyn A1 - Séverine Goscinny A1 - De Spiegeleer, Bart A1 - Celine Vanhee A1 - Eric Deconinck AB -

Advances in biotechnology and the chemical synthesis of peptides have made biopharmaceuticals and synthetic peptide drugs viable pharmaceutical compounds today and an important source for tomorrow's drugs and therapies. Unfortunately, also falsifications and counterfeit versions of these powerful and promising drugs are offered illegally via the internet. Since these falsified preparations are produced outside the legally required quality systems, end-users have no guarantee regarding the efficacy and safety of these products. Although falsified samples of biotherapeutics were already analysed, looking at a specific aspect of their quality or identity, no systematic studies have been performed regarding the presence of different impurities or possible contaminations. Therefore, in order to obtain a better understanding of the potential health risks related to the usage of falsified polypeptide drugs we performed a systematic screening of the ten most frequently encountered falsified peptide drugs on the Belgian market acquired from three different suspected illegal internet pharmacies. The screening incorporated the analysis of the active pharmaceutical ingredient (API), API-related impurities, small molecule contaminants (defined as organic small molecules not belonging to the other categories), elemental impurities and residual solvents. This comprehensive study showed that these type of falsified drugs not only have a high variation in amount of drugs per unit and a low purity (ranging between 5% and 75% for cysteine containing peptides), but also contained the known toxic class one elemental impurities arsenic (As) and lead (Pb). One sample was contaminated with Pb while multiple samples were found with concentrations up to ten times the ICH toxicity limit for parenteral drugs. Subsequent speciation of As confirmed the elevated concentrations for As and demonstrated that all As was present in the more toxic inorganic form. Together with the (sometimes) high amount of peptide impurities and the inherent dangers associated with the use of unauthorized peptide drugs (such as doping peptides or preclinical drugs) this study confirms the reported potential health risks patients/users take when resorting to falsified peptide drugs. Moreover, the presence of the carcinogen As and the known accumulation in human tissues of Pb raises questions about potential sub-acute to chronic toxicity due to the long term administration of these falsified peptide drugs.

VL - 188 M3 - 10.1016/j.talanta.2018.06.023 ER - TY - Generic T1 - MSSFP04: Sildenafil Study Y1 - 2018 A1 - Eric Deconinck A1 - Marie Bertrand JF - API-WG meeting CP - EDQM ER - TY - Generic T1 - MSSIP05 Y1 - 2018 A1 - Eric Deconinck A1 - Marie Bertrand JF - Counterfeit Wg meeting CP - EDQM ER - TY - THES T1 - Ontwikkeling en validatie van een HS-GC-MS/MS methode voor de bepaling van potentieel genotoxische smaakstoffen in e-vloeistoffen. Y1 - 2018 A1 - Sanae El Merabety A1 - Sophia Barhdadi A1 - Eric Deconinck KW - undefined PB - Vrije Universiteit Brussel CY - Brussels ER - TY - Generic T1 - Proposal MSSIP 05: Designer molecules and non-INN drugs in medicines and dietary supplements Y1 - 2018 A1 - Eric Deconinck JF - Counterfeit WG Meeting EDQM CY - Sarajevo, Bosmie-Herzegovina CP - EDQM ER - TY - THES T1 - Screening van recreationele drugs en kwalificatie en kwantificatie van MDMA met behulp van infrarood (IR)-technieken en chemometrische modellen Y1 - 2018 A1 - Raf Van Campenhout A1 - Eric Deconinck KW - Chemometrics KW - IR KW - Recreative drugs PB - Vrije Universiteit Brussel CY - Brussels, Belgium ER - TY - Generic T1 - the threat of illegal herbal medicines Y1 - 2018 A1 - Eric Deconinck KW - herbal medicines KW - illegal plants JF - DA-PBA 2018 CP - BGFW-KULeuven ER - TY - JOUR T1 - Analysis of illegal peptide drugs via HILIC-DAD-MS. JF - Talanta Y1 - 2017 A1 - Steven Janvier A1 - De Sutter, Evelien A1 - Wynendaele, Evelien A1 - De Spiegeleer, Bart A1 - Celine Vanhee A1 - Eric Deconinck AB -

Biopharmaceuticals have established themselves as highly efficient medicines, and are still one of the fastest growing parts of the health-product industry. Unfortunately, the introduction of these promising new drugs went hand in hand with the creation of a black market for illegal and counterfeit biotechnology drugs. Particularly popular are the lyophilised peptides with a molecular weight of less than 5kDa. Most of them are meant for subcutaneous injection and are easily accessible via the internet. In recent years, different methods based on reversed phase liquid chromatography have been developed to detect and quantify these peptides. The emerging of more polar peptides however requires the introduction of other separation techniques. Therefore, we set out to develop and validate an analytical method based on hydrophilic interaction liquid chromatography (HILIC) to identify and quantify the most frequently encountered illegal peptides on the European market. For this objective, five different HILIC columns were selected and screened for their chromatographic performance. Among those columns, the ZIC HILIC column showed the best performance under the tested screening conditions in terms of resolution and symmetry factor for the targeted peptide set. Hence, the operational conditions were further optimised for the identification of illegal preparations via mass spectrometry (MS) and quantification via UV. Validation was performed via accuracy profiles based on the ISO 17025 guideline. The obtained validated HILIC-method allows for the detection and quantification of the most frequently encountered illegal peptides on the internet in a total run time of 35min including post gradient equilibration and online cleaning step. Combined with a previously developed RPLC-method, the ZIC HILIC system allows for the detection and quantification of a wide spectrum of illicit peptide drugs available on the internet. Furthermore, the developed method could also be envisaged for the detection of new emerging polar peptide drugs.

VL - 174 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28738623?dopt=Abstract M3 - 10.1016/j.talanta.2017.06.034 ER - TY - Generic T1 - API-WG project: Chemometric Results: Atorvastatin Y1 - 2017 A1 - Eric Deconinck KW - API fingerprinting KW - Chemometrics JF - API-working group PB - EDQM CY - Strasbourg, France CP - EDQM ER - TY - JOUR T1 - Are injectable illegal polypeptide drugs safe? Case report demonstrating the presence of haemolytic Bacillus cereus in two illegal peptide drugs. JF - Drug Testing and Analysis Y1 - 2017 A1 - Steven Janvier A1 - Elke Wattijn A1 - N Botteldoorn A1 - De Spiegeleer, Bart A1 - Eric Deconinck A1 - Celine Vanhee KW - Bacillus cereus KW - Bacterial Toxins KW - Illegal biopharmaceuticals KW - Sterility M3 - 10.1002/dta.2304 ER - TY - Generic T1 - Authenticity checks in Belgium Y1 - 2017 A1 - Eric Deconinck KW - authenticity checks KW - Counterfeit medicines JF - CAP-meeting PB - EDQM CY - Karlsrühe, Germany CP - EDQM ER - TY - Generic T1 - Authenticity checks of medicines in Belgium Y1 - 2017 A1 - Eric Deconinck KW - Counterfeit medicines JF - CAP meeting PB - EDQM CY - Karlsrühe, Germany CP - EDQM ER - TY - JOUR T1 - Chemometrical analysis of fingerprints for the detection of counterfeit and falsified medicines JF - Reviews in Analytical Chemistry Y1 - 2017 A1 - Custers,D. A1 - Patricia Courselle A1 - Apers,S A1 - Eric Deconinck KW - aims KW - an KW - analysi KW - analysis KW - AS KW - at KW - Chemometrics KW - Control KW - Counterfeit KW - Counterfeit medicines KW - data KW - detection KW - health KW - Literature KW - Medicine KW - Multivariate KW - ON KW - Practice KW - PRACTICES KW - public KW - public health KW - Public-health KW - Quality KW - Quality Control KW - Quantification KW - Research KW - REVIEW KW - SAFETY KW - Sample KW - successful KW - use AB -

Counterfeit medicines pose a major threat topublic health worldwide. These pharmaceuticals aremostly manufactured without respecting Good ManufacturingPractices. Moreover, they are not subjected to anyform of quality control, and therefore their safety, efficacy,and quality cannot be guaranteed. Extensive research oncounterfeit medicines has already been performed andpublished in literature. This review aims at providing anupdated overview of the use of fingerprints and subsequentmultivariate (chemometrical) data analysis in thefield of counterfeit medicine detection. Fingerprintingcould be a useful tool in the analysis of counterfeit medicinesbecause it generates a holistic view of a sample,rather than focusing on specific and predefined characteristics,such as identification and quantification of presentactive pharmaceutical ingredients. This review firstprovides an introduction into the counterfeiting problem.Next, the concept of fingerprinting and the basicprinciples of chemometrics are explained, followed by adescription of the successful application of fingerprints inthe field of Pharmacognosy. The last part of this reviewprovides an overview describing the use of fingerprints incounterfeit medicine research.

VL - 35 U1 - 2677 M3 - doi:10.1515/REVAC-2016-0013 ER - TY - JOUR T1 - Chemometrics and chromatographic fingerprints to classify plant food supplements according to the content of regulated plants. JF - J Pharm Biomed Anal Y1 - 2017 A1 - Eric Deconinck A1 - C A Sokeng Djiogo A1 - Patricia Courselle AB -

Plant food supplements are gaining popularity, resulting in a broader spectrum of available products and an increased consumption. Next to the problem of adulteration of these products with synthetic drugs the presence of regulated or toxic plants is an important issue, especially when the products are purchased from irregular sources. This paper focusses on this problem by using specific chromatographic fingerprints for five targeted plants and chemometric classification techniques in order to extract the important information from the fingerprints and determine the presence of the targeted plants in plant food supplements in an objective way. Two approaches were followed: (1) a multiclass model, (2) 2-class model for each of the targeted plants separately. For both approaches good classification models were obtained, especially when using SIMCA and PLS-DA. For each model, misclassification rates for the external test set of maximum one sample could be obtained. The models were applied to five real samples resulting in the identification of the correct plants, confirmed by mass spectrometry. Therefore chromatographic fingerprinting combined with chemometric modelling can be considered interesting to make a more objective decision on whether a regulated plant is present in a plant food supplement or not, especially when no mass spectrometry equipment is available. The results suggest also that the use of a battery of 2-class models to screen for several plants is the approach to be preferred.

VL - 143 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28554127?dopt=Abstract M3 - 10.1016/j.jpba.2017.05.032 ER - TY - JOUR T1 - Chromatographic fingerprinting as a strategy to identify regulated plants in illegal herbal supplements. JF - Talanta Y1 - 2017 A1 - Custers, D A1 - Van Praag, N A1 - Patricia Courselle A1 - Apers, S A1 - Eric Deconinck AB -

Erectile dysfunction (ED) is a sexual disorder characterized by the inability to achieve or maintain a sufficiently rigid erection. Despite the availability of non-invasive oral treatment options, many patients turn to herbal alternatives. Furthermore, herbal supplements are increasingly gaining popularity in industrialized countries and, as a consequence, quality control is a highly important issue. Unfortunately, this is not a simple task since plants are often crushed and mixed with other plants, which complicates their identification by usage of classical approaches such as microscopy. The aim of this study was to explore the potential use of chromatographic fingerprinting to identify plants present in herbal preparations intended for the treatment of ED. To achieve this goal, a HPLC-PDA and a HPLC-MS method were developed, using a full factorial experimental design in order to acquire characteristic fingerprints of three plants which are potentially beneficial for treating ED: Epimedium spp., Pausinystalia yohimbe and Tribulus terrestris. The full factorial design demonstrated that for all three plant references a C8 column (250mm×4.6mm; 5µm particle size) is best suited; methanol and an ammonium formate buffer (pH 3) were found to be the best constituents for the mobile phase. The suitability of this strategy was demonstrated by analysing several self-made triturations in three different botanical matrices, which mimic the influential effects that could be expected when analysing herbal supplements. To conclude, this study demonstrates that chromatographic fingerprinting could provide a useful means to identify plants in a complex herbal mixture.

VL - 164 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28107963?dopt=Abstract M3 - 10.1016/j.talanta.2016.12.008 ER - TY - JOUR T1 - Clustering and diagnostic modelling of slimming aids based on chromatographic and mass spectrometric fingerprints JF - Drug Test Anal Y1 - 2017 A1 - Custers, D A1 - Els Van Hoeck A1 - Patricia Courselle A1 - Apers, S A1 - Eric Deconinck KW - Anti-Obesity Agents KW - Chromatography, High Pressure Liquid KW - Cluster Analysis KW - Discriminant Analysis KW - Least-Squares Analysis KW - Mass Spectrometry KW - Principal Component Analysis AB -

Herbal medicines and food supplements intended as slimming aids are increasingly gaining popularity worldwide, especially for treating obesity. In this study, an ultra-performance liquid chromatography coupled to photodiode array detection (UPLC-PDA) and an ultra-performance liquid chromatography mass spectrometry (UPLC-MS) method were developed to analyze 92 slimming aids (confiscated by customs), aimed at acquiring highly informative fingerprints. Three types of fingerprints were acquired (PDA, Total Ion Chromatograms (TIC), and MS fingerprints) which were used in the chemometric data analysis. Both unsupervised (i.e., Hierarchical Cluster Analysis (HCA)) and supervised techniques (i.e., Classification and Regression Tree (CART) and Partial Least Squares - Discriminant Analysis (PLS-DA)) were applied. The aim was to perform an in-depth study of the samples, thereby exploring potential patterns present in the data. HCA was able to generate a clustering which was mainly defined by chemical compounds detected in the samples, i.e., sibutramine, phenolphthalein and amfepramone. PLS-DA generated the best diagnostic models for both PDA and TIC fingerprints, characterized by correct classification rates of external validation of 85% and 80%, respectively. For the MS fingerprints, the best model was obtained by CART (65% correct classification rate of external validation). Despite a lower correct classification rate, exploration of the concerned misclassifications revealed that the MS fingerprints proved to be superior since even very low concentrations of sibutramine could be detected. This study shows that reliable chemometric models can be obtained, based on the presence of prohibited chemical substances, which allow high-throughput data analysis of such samples. Moreover, they generate a prime notion of potential threat to a patient's health posed by these kinds of slimming aids. Copyright © 2016 John Wiley & Sons, Ltd.

VL - 9 CP - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27006262?dopt=Abstract M3 - 10.1002/dta.1964 ER - TY - Generic T1 - Decision tree for specific chemometric methods Y1 - 2017 A1 - Eric Deconinck KW - API fingerprinting KW - Chemometrics JF - API-working group of the GEON network, EDQM T3 - API-WG PB - EDQM CY - Strasbourg, France CP - EDQM ER - TY - JOUR T1 - Detection of regulated herbs and plants in plant food supplements and traditional medicines using infrared spectroscopy. JF - J Pharm Biomed Anal Y1 - 2017 A1 - Eric Deconinck A1 - C A Sokeng Djiogo A1 - Bothy, J L A1 - Patricia Courselle AB -

The identification of a specific toxic or regulated plant in herbal preparations or plant food supplements is a real challenge, since they are often powdered, mixed with other herbal or synthetic powders and compressed into tablets or capsules. The classical identification approaches based on micro- and macroscopy are therefore not possible anymore. In this paper infrared spectroscopy, combined with attenuated total reflectance was evaluated for the screening of plant based preparations for nine specific plants (five regulated and four common plants for herbal supplements). IR and NIR spectra were recorded for a series of self-made triturations of the targeted plants. After pretreatment of the spectral data chemometric classification techniques were applied to both data sets (IR and NIR) separately and the combination of both. The results show that the screening of herbal preparations or plant food supplements for specific plants, using infrared spectroscopy, is feasible. The best model was obtained with the Mid-IR data, using SIMCA as modelling technique. During validation of the model, using an external test set, 21 of 25 were correctly classified and six of the nine targeted plants showed no misclassifications for the selected test set. For the other three a success rate of 50% was obtained. Mid-IR combined with SIMCA can therefore be applied as a first step in the screening of unknown samples, before applying more sophisticated fingerprint approaches or identification tests described in several national and international pharmacopoeia. As a proof of concept five real suspicious samples were successfully screened for the targeted regulated plants.

VL - 142 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28521274?dopt=Abstract M3 - 10.1016/j.jpba.2017.04.051 ER - TY - JOUR T1 - Development and validation of a HS/GC-MS method for the simultaneous analysis of diacetyl and acetylpropionyl in electronic cigarette refills JF - J.Pharm.Biomed.Anal. Y1 - 2017 A1 - Sophia Barhdadi A1 - Michael Canfyn A1 - Patricia Courselle A1 - Rogiers,V. A1 - Vanhaecke,T. A1 - Eric Deconinck KW - Analyses KW - analysi KW - analysis KW - approach KW - AS KW - Belgium KW - bias KW - Brussels KW - Control KW - Development KW - electronic KW - EVALUATION KW - food KW - health KW - identify KW - Institute KW - IS KW - journal KW - measurement KW - Medicine KW - method KW - methodology KW - methods KW - ON KW - profile KW - public KW - public health KW - Public-health KW - Quality KW - Quality Control KW - Quantification KW - SAFETY KW - Sample KW - Samples KW - SCREENING KW - study KW - tobacco KW - toxicity KW - Toxicology KW - use KW - VALIDATION AB -

The use of e-cigarettes as alternative for tobacco cigarettes has become increasingly popular, even though their safety has not yet been scientifically established. One of the frequently raised concerns is the potential toxicity of certain flavours present in the e-liquids, such as diacetyl and acetylpropionyl. It is therefore important to be able to identify and quantify both compounds. Numerous analytical methods have been published for determining e-liquid compositions, but concerns exist with respect to the lack of analytical evaluation. Hence in this study, a new HS/GC-MS-based method was developed for the screening and quantification of diacetyl and acetylpropionyl in e-liquids. This method was fully validated using the 'total error' approach. The LOQ of the analytical method was 5ppm for diacetyl and acetylpropionyl. The obtained accuracy profiles show that the beta-expectation tolerance intervals did not exceed the acceptance limits of+/-10%, meaning that 95% of future measurements will be included in the [-10%, 10%] bias limits. As proof of applicability, the validated method was successfully applied on a small set of e-liquid samples, indicating that this methodology could be used for routine quality control analyses of e-liquids

VL - 142 U1 - 2682 M3 - S0731-7085(16)31467-4 [pii];10.1016/j.jpba.2017.04.050 [doi] ER - TY - Generic T1 - Identification and quantification of falsified peptide drugs via HILIC-DAD-MS Y1 - 2017 A1 - Steven Janvier A1 - Evelien de Sutter A1 - Bart de Spiegeleer A1 - Celine Vanhee A1 - Eric Deconinck ER - TY - JOUR T1 - Identification of epidermal growth factor (EGF), in an unknown pharmaceutical preparation suspected to contain insulin like growth factor 1 (IGF-1). JF - Drug Test Anal Y1 - 2017 A1 - Celine Vanhee A1 - Steven Janvier A1 - Moens, Goedele A1 - Séverine Goscinny A1 - Patricia Courselle A1 - Eric Deconinck KW - EGF KW - epidermal growth factor KW - IGF-1 KW - insulin like growth factor 1 KW - pharmaceutical preparation VL - 9 CP - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27390261?dopt=Abstract M3 - 10.1002/dta.2029 ER - TY - Generic T1 - Medicines in disguise: situation & challenges Y1 - 2017 A1 - Eric Deconinck KW - analysi KW - analysis KW - challenge KW - food KW - Food Analysis KW - Medicine KW - situation KW - trend KW - trends JF - Trends in food analysis PB - NA CY - NA CP - KVCV U1 - 2688 U2 - 24/05/2017 ER - TY - BOOK T1 - Nutritional Modeulators of Pain in the Aging Population T2 - Illegal Adulterations of (Traditional) herbal Medicines and Dietary Supplements for the treatment of pain Y1 - 2017 A1 - Eric Deconinck KW - dietary KW - Medicine KW - POPULATION KW - treatment JF - Illegal Adulterations of (Traditional) herbal Medicines and Dietary Supplements for the treatment of pain PB - Academic Press Elsevier CY - London, UK VL - 298 SN - 978-0-12-805186-3 ER - TY - Generic T1 - Pharmaceutical crime from a laboratory point of view Y1 - 2017 A1 - Eric Deconinck ED - VUB KW - Counterfeit KW - Faculty KW - Laboratories KW - Science JF - Doctoral seminar, Faculty of Pharmaceutical Sciences, KUL CP - Adams,E., Van Schepdael,A. U1 - 2678 U2 - 30/05/2016 ER - TY - Generic T1 - The possibilities of chemometrics in API and counterfeit testing Y1 - 2017 A1 - Eric Deconinck KW - Chemometrics KW - Counterfeit JF - Counterfeit Symposium EDQM PB - NA CY - NA CP - EDQM U1 - 2679 U2 - 28-29/03/2017 ER - TY - JOUR T1 - The use of Stationary Phase Optimized Selectivity Liquid Chromatography for the development of herbal fingerprints to detect targeted plants in plant food supplements. JF - Talanta Y1 - 2017 A1 - Eric Deconinck A1 - C A Sokeng Djiogo A1 - Angelique Kamugisha A1 - Patricia Courselle KW - ALL KW - AS KW - Belgium KW - Brussels KW - care KW - chromatography KW - Combination KW - CONSUMPTION KW - Control KW - detection KW - Development KW - electronic KW - food KW - health KW - health care KW - HEALTH-CARE KW - Institute KW - IS KW - journal KW - liquid chromatography KW - Literature KW - Medicine KW - national KW - ON KW - plant KW - Plants KW - PRODUCTS KW - public KW - public health KW - Public-health KW - Quality KW - Quality Control KW - SAFETY KW - Sample KW - Samples KW - Type KW - use AB -

The consumption of plant food supplements is increasing steadily and more and more, these products are bought through internet. Often the products sold through internet are not registered or declared with a national authority, meaning that no or minimal quality control is performed and that they could contain herbs or plants that are regulated. Stationary Phase Optimized Selectivity Liquid Chromatography (SOS-LC) was evaluated for the development of specific fingerprints, to be used for the detection of targeted plants in plant food supplements. Three commonly used plants in plant food supplements and two regulated plants were used to develop fingerprints with SOS-LC. It was shown that for all plants specific fingerprints could be obtained, allowing the detection of these targeted plants in triturations with different herbal matrices as well as in real samples of suspicious supplements seized by the authorities. For three of the five plants a more specific fingerprint was obtained, compared to the ones developed on traditional columns described in literature. It could therefore be concluded that the combination of segments of different types of stationary phases, as used in SOS-LC, has the potential of becoming a valuable tool in the quality control and the identification of crude herbal or plant material and in the detection of regulated plants in plant food supplements or other herbal preparations.

VL - 170 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28501194?dopt=Abstract M3 - 10.1016/j.talanta.2017.04.028 ER - TY - THES T1 - Wat zit er achter poeders, kleuren en logo's: sceening van illegale drugs op zomerfestivals Y1 - 2017 A1 - Kevin Huysegoms A1 - Eric Deconinck PB - VUB CY - Jette ER - TY - Generic T1 - API WG project: Chemometric results for Atorvastatin Y1 - 2016 A1 - Eric Deconinck A1 - Acevska,J. KW - Counterfeit KW - result KW - results KW - working group JF - Counterfeit Working Group PB - NA CY - NA CP - EDQM U1 - 2669 U2 - 17/11/2016 ER - TY - JOUR T1 - Chemometrics and the identification of counterfeit medicines-A review. JF - J Pharm Biomed Anal Y1 - 2016 A1 - Krakowska, B A1 - Custers, D A1 - Eric Deconinck A1 - Daszykowski, M KW - Chemistry Techniques, Analytical KW - Cluster Analysis KW - Counterfeit Drugs KW - Discriminant Analysis KW - Drug Contamination KW - Models, Theoretical KW - Pattern Recognition, Automated AB -

This review article provides readers with a number of actual case studies dealing with verifying the authenticity of selected medicines supported by different chemometric approaches. In particular, a general data processing workflow is discussed with the major emphasis on the most frequently selected instrumental techniques to characterize drug samples and the chemometric methods being used to explore and/or model the analytical data. However, further discussion is limited to a situation in which the collected data describes two groups of drug samples - authentic ones and counterfeits.

VL - 127 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27133184?dopt=Abstract M3 - 10.1016/j.jpba.2016.04.016 ER - TY - JOUR T1 - Chromatographic impurity fingerprinting of genuine and counterfeit Cialis® as a means to compare the discriminating ability of PDA and MS detection. JF - Talanta Y1 - 2016 A1 - Custers, D A1 - Krakowska, B A1 - De Beer, J O A1 - Patricia Courselle A1 - Daszykowski, M A1 - Apers, S A1 - Eric Deconinck KW - Chromatography, High Pressure Liquid KW - Counterfeit Drugs KW - Informatics KW - Machine Learning KW - Mass Spectrometry KW - Principal Component Analysis KW - Tadalafil AB -

Public health is threatened worldwide by counterfeit medicines. Their quality, safety and efficacy cannot be guaranteed since no quality control is performed during and/or after the manufacturing process. Characterization of these products is a very important topic. During this study a High Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) and a High Performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) method were developed to analyse both genuine and counterfeit samples of Cialis®. The obtained PDA and MS fingerprints were explored and modelled using unsupervised Principal Component Analysis (PCA) and supervised Partial Least Squares and its discriminant variant (PLS, PLS-DA) as well the classification methods including Soft Independent Modelling of Class Analogy (SIMCA) and the k Nearest Neighbour classifier (kNN). Both MS1 and MS2 data and data measured at 254 nm and 270 nm were used with the aim to test the potential complementarity of PDA and MS detection. First, it was checked if both groups of fingerprints can support differentiation between genuine and counterfeit medicines. Then, it was verified if the obtained multivariate models could be improved by combining information present in MS and PDA fingerprints. Survey of the models obtained for the 254 nm data, 270 nm data and 254_270 nm data combination showed that a tendency of discrimination could be observed with PLS. For the 270 nm data and 254_270 nm data combination a perfect discrimination between genuine and counterfeit medicines is obtained with PLS-DA and SIMCA. This shows that 270 nm alone performs equally well compared to 254_270 nm. For the MS1 and MS1_MS2 data perfect models were obtained using PLS-DA and kNN, indicating that the MS2 data do not provide any extra useful information to acquire the aimed distinction. When combining MS1 and 270 nm perfect models were gained by PLS-DA and SIMCA, which is very similar to the results obtained for PDA alone. These results show that both detectors have a potential to reveal chemical differences between genuine and counterfeit medicines and thus enable the construction of diagnostic models with excellent recognition. However, if a larger sample set, including more possible sources of variation, is analysed more sophisticated techniques such as MS might be necessary.

VL - 146 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26695302?dopt=Abstract M3 - 10.1016/j.talanta.2015.09.029 ER - TY - JOUR T1 - Comparison of three development approaches for Stationary Phase Optimised Selectivity Liquid Chromatography based screening methods Part II: A group of structural analogues (PDE-5 inhibitors in food supplements). JF - Talanta Y1 - 2016 A1 - Eric Deconinck A1 - Ghijs, L A1 - Angelique Kamugisha A1 - Patricia Courselle KW - Chemistry, Pharmaceutical KW - Chromatography, Liquid KW - Dietary Supplements KW - Food Contamination KW - Pesticide residues KW - Phosphodiesterase 5 Inhibitors AB -

Three approaches for the development of a screening method to detect adulterated dietary supplements, based on Stationary Phase Optimised Selectivity Liquid Chromatography were compared for their easiness/speed of development and the performance of the optimal method obtained. This comparison was performed for a heterogeneous group of molecules, i.e. slimming agents (Part I) and a group of structural analogues, i.e. PDE-5 inhibitors (Part II). The first approach makes use of primary runs at one isocratic level, the second of primary runs in gradient mode and the third of primary runs at three isocratic levels to calculate the optimal combination of segments of stationary phases. In each approach the selection of the stationary phase was followed by a gradient optimisation. For the PDE-5 inhibitors, the group of structural analogues, only the method obtained with the third approach was able to differentiate between all the molecules in the development set. Although not all molecules are baseline separated, the method allows the identification of the selected adulterants in dietary supplements using only diode array detection. Though, due to the mobile phases used, the method could also be coupled to mass spectrometry. The method was validated for its selectivity following the guidelines as described for the screening of pesticide residues and residues of veterinary medicines in food.

VL - 148 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26653459?dopt=Abstract M3 - 10.1016/j.talanta.2015.10.065 ER - TY - JOUR T1 - Comparison of three development approaches for Stationary Phase Optimised Selectivity Liquid Chromatography based screening methods Part I: A heterogeneous group of molecules (slimming agents in food supplements). JF - Talanta Y1 - 2016 A1 - Eric Deconinck A1 - Ghijs, L A1 - Angelique Kamugisha A1 - Patricia Courselle KW - Appetite Depressants KW - Chemistry, Pharmaceutical KW - Chromatography, High Pressure Liquid KW - Chromatography, Liquid KW - Dietary Supplements KW - Food Contamination AB -

Three approaches for the development of a screening method to detect adulterated dietary supplement, based on Stationary Phase Optimised Selectivity Liquid Chromatography were compared for their easiness/speed of development and the performance of the optimal method obtained. This comparison was performed for a heterogeneous group of molecules, i.e. slimming agents (Part I) and a group of structural analogues, i.e. PDE-5 inhibitors (Part II). The first approach makes use of primary runs at one isocratic level, the second of primary runs in gradient mode and the third of primary runs at three isocratic levels to calculate the optimal combination of segments of stationary phases. In each approach the selection of the stationary phase was followed by a gradient optimisation. For the slimming agents, the heterogeneous group of molecules, the method obtained with the first approach was selected as optimal, based on the speed of development and the performance of the method. The method shows a good separation of the compounds, allowing the screening to be performed with diode array detection, and is fully compatible with mass spectrometry. The method was validated for its selectivity following the guidelines as described for the screening of pesticide residues and residues of veterinary medicines in food.

VL - 148 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26653480?dopt=Abstract M3 - 10.1016/j.talanta.2015.10.066 ER - TY - JOUR T1 - Discriminating nicotine and non-nicotine containing e-liquids using infrared spectroscopy. JF - J Pharm Biomed Anal Y1 - 2016 A1 - Eric Deconinck A1 - Bothy, J L A1 - Sophia Barhdadi A1 - Patricia Courselle KW - Belgium KW - Electronic Cigarettes KW - Nicotine KW - Spectroscopy, Near-Infrared AB -

In a few countries, including Belgium, nicotine-containing e-cigarettes and e-liquids are considered medicines, and therefore cannot freely be sold, but should be distributed in a pharmacy. The fact that in the neighbouring countries these products are freely available, poses a problem for custom personnel, the more the nicotine content of the products is not always labelled, especially when they are bought through internet. Therefore there is a need for easy-to-use equipment and methods to perform a first on site screening of intercepted samples, both for border control as to check label compliance of the sample. The use of attenuated total reflectance-infrared spectroscopy (ATR-IR) and near infrared spectroscopy (NIR), combined with chemometrics was evaluated for the discrimination between nicotine containing and non-nicotine containing samples. It could be concluded that both ATR-IR and NIR could be used for the discrimination when combined with the appropriate chemometric techniques. The presented techniques do not need sample preparation and result in models with a minimum of false negative samples. If a large enough training set can be established the interpretation can be fully automated, making the presented approach suitable for on-site screening of e-liquid samples.

VL - 120 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26771132?dopt=Abstract M3 - 10.1016/j.jpba.2015.12.054 ER - TY - JOUR T1 - In vitro Dermal Absorption of Hydroquinone: Protocol Validation and Applicability on Illegal Skin-Whitening Cosmetics. JF - Skin Pharmacol Physiol Y1 - 2016 A1 - Bart Desmedt A1 - Ates, Gamze A1 - Patricia Courselle A1 - De Beer, Jacques O A1 - Rogiers, Vera A1 - Hendrickx, Benoit A1 - Eric Deconinck A1 - De Paepe, Kristien KW - Adult KW - Drug and Narcotic Control KW - Female KW - Humans KW - Hydroquinones KW - In Vitro Techniques KW - Male KW - middle aged KW - Reproducibility of Results KW - SKIN KW - Skin Absorption KW - Skin Lightening Preparations KW - Temperature AB -

In Europe, hydroquinone is a forbidden cosmetic ingredient. It is, however, still abundantly used because of its effective skin-whitening properties. The question arises as to whether the quantities of hydroquinone used become systemically available and may cause damage to human health. Dermal absorption studies can provide this information. In the EU, dermal absorption has to be assessed in vitro since the Cosmetic Regulation 1223/2009/EC forbids the use of animals. To obtain human-relevant data, a Franz diffusion cell protocol was validated using human skin. The results obtained were comparable to those from a multicentre validation study. The protocol was applied to hydroquinone and the dermal absorption ranged between 31 and 44%, which is within the range of published in vivo human values. This shows that a well-validated in vitro dermal absorption study using human skin provides relevant human data. The validated protocol was used to determine the dermal absorption of illegal skin-whitening cosmetics containing hydroquinone. All samples gave high dermal absorption values, rendering them all unsafe for human health. These results add to our knowledge of illegal cosmetics on the EU market, namely that they exhibit a negative toxicological profile and are likely to induce health problems.

VL - 29 CP - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28052295?dopt=Abstract M3 - 10.1159/000454719 ER - TY - Generic T1 - Medicines in disguise: situation and challenges (Plenary Lecture) Y1 - 2016 A1 - Eric Deconinck KW - challenge KW - Medicine KW - Science KW - situation JF - 19th forum of Pharmaceutical Sciences PB - NA CY - NA CP - BGFW U1 - 2634 U2 - october 17-19th ER - TY - JOUR T1 - The Monte Carlo validation framework for the discriminant partial least squares model extended with variable selection methods applied to authenticity studies of Viagra® based on chromatographic impurity profiles. JF - Analyst Y1 - 2016 A1 - Krakowska, B A1 - Custers, D A1 - Eric Deconinck A1 - Daszykowski, M KW - chromatography KW - Counterfeit Drugs KW - Discriminant Analysis KW - Least-Squares Analysis KW - Monte Carlo Method KW - Sildenafil Citrate AB -

The aim of this work was to develop a general framework for the validation of discriminant models based on the Monte Carlo approach that is used in the context of authenticity studies based on chromatographic impurity profiles. The performance of the validation approach was applied to evaluate the usefulness of the diagnostic logic rule obtained from the partial least squares discriminant model (PLS-DA) that was built to discriminate authentic Viagra® samples from counterfeits (a two-class problem). The major advantage of the proposed validation framework stems from the possibility of obtaining distributions for different figures of merit that describe the PLS-DA model such as, e.g., sensitivity, specificity, correct classification rate and area under the curve in a function of model complexity. Therefore, one can quickly evaluate their uncertainty estimates. Moreover, the Monte Carlo model validation allows balanced sets of training samples to be designed, which is required at the stage of the construction of PLS-DA and is recommended in order to obtain fair estimates that are based on an independent set of samples. In this study, as an illustrative example, 46 authentic Viagra® samples and 97 counterfeit samples were analyzed and described by their impurity profiles that were determined using high performance liquid chromatography with photodiode array detection and further discriminated using the PLS-DA approach. In addition, we demonstrated how to extend the Monte Carlo validation framework with four different variable selection schemes: the elimination of uninformative variables, the importance of a variable in projections, selectivity ratio and significance multivariate correlation. The best PLS-DA model was based on a subset of variables that were selected using the variable importance in the projection approach. For an independent test set, average estimates with the corresponding standard deviation (based on 1000 Monte Carlo runs) of the correct classification rate, sensitivity, specificity and area under the curve were equal to 96.42% ± 2.04, 98.69% ± 1.38, 94.16% ± 3.52 and 0.982 ± 0.017, respectively.

VL - 141 CP - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26730545?dopt=Abstract M3 - 10.1039/c5an01656h ER - TY - JOUR T1 - Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe. JF - J Eur Acad Dermatol Venereol Y1 - 2016 A1 - Bart Desmedt A1 - Patricia Courselle A1 - De Beer, J O A1 - Rogiers, V A1 - Grosber, M A1 - Eric Deconinck A1 - De Paepe, K KW - Cosmetics KW - Europe KW - Humans KW - Skin Lightening Preparations KW - Skin Pigmentation AB -

Lightening skin tone is an ancient and well-documented practice, and remains common practice among many cultures. Whitening agents such as corticosteroids, tretinoin and hydroquinone are medically applied to effectively lighten the skin tone of hyperpigmented lesions. However, when these agents are used cosmetically, they are associated with a variety of side-effect. Alternative agents, such as arbutin and its derivatives kojic acid and nicotinamide have been subsequently developed for cosmetic purposes. Unfortunately, some cosmetics contain whitening agents that are banned for use in cosmetic products. This article provides an overview of the mode of action and potential side-effects of cosmetic legal and illegal whitening agents, and the pattern of use of these types of products. Finally, an EU analysis of the health problems due to the presence of illegal products on the market is summarized.

VL - 30 CP - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26953335?dopt=Abstract M3 - 10.1111/jdv.13595 ER - TY - JOUR T1 - Physical profiling and IR spectroscopy: simple and effective methods to discriminate between genuine and counterfeit samples of Viagra® and Cialis®. JF - Drug Test Anal Y1 - 2016 A1 - Custers, Deborah A1 - Vandemoortele, Suzanne A1 - Bothy, Jean-Luc A1 - De Beer, Jacques O A1 - Patricia Courselle A1 - Apers, Sandra A1 - Eric Deconinck KW - Counterfeit Drugs KW - Drug Packaging KW - Least-Squares Analysis KW - Principal Component Analysis KW - Reproducibility of Results KW - Sildenafil Citrate KW - Spectrophotometry, Infrared KW - Tablets KW - Tadalafil AB -

Counterfeit medicines are a global threat to public health. High amounts enter the European market, enforcing the need for simple techniques to help customs detect these pharmaceuticals. This study focused on physical profiling and IR spectroscopy to obtain a prime discrimination between genuine and illegal Viagra® and Cialis® medicines. Five post-tableting characteristics were explored: colour, mass, long length, short length, and thickness. Hypothesis testing showed that most illegal samples (between 60 and 100%) significantly differ from the genuine medicines, in particular for mass and long length. Classification and Regression Trees (CART) analysis resulted in a good discrimination between genuine and illegal medicines (98.93% correct classification rate for Viagra®, 99.42% for Cialis®). Moreover, CART confirmed the observation that mass and long length are the key physical characteristics which determine the observed discrimination. IR analysis was performed on tablets without blister and on tablets in intact blister. These data were analyzed using Soft Independent Modelling of Class Analogy (SIMCA) and Partial Least Squares - Discriminant Analysis (PLS-DA). Supervised techniques needed to be applied since Principal Component Analysis (PCA) was not able to generate the desired discrimination. Our study shows that a perfect discrimination between genuine and illegal medicines can be made by both SIMCA and PLS-DA without removing the tablets from the blister. This approach has the advantage of keeping the blister intact. Our study demonstrates that these user friendly techniques are reliable methods to aid customs to obtain a prime distinction between genuine and illegal samples on the spot. Copyright © 2015 John Wiley & Sons, Ltd.

VL - 8 CP - 3-4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26033891?dopt=Abstract M3 - 10.1002/dta.1813 ER - TY - JOUR T1 - A simple dilute and shoot methodology for the identification and quantification of illegal insulin JF - Journal of Pharmaceutical Analysis Y1 - 2016 A1 - Celine Vanhee A1 - Steven Janvier A1 - Moens,G. A1 - Eric Deconinck A1 - Patricia Courselle KW - illegal insulin KW - LC–DAD–MS/MS KW - Quantification method KW - Screening method AB -

The occurrence of illegal medicines is a well-established global problem and concerns mostly small molecules. However, due to the advances in genomics and recombinant expression technologies there is an increased development of polypeptide therapeutics. Insulin is one of the best known polypeptide drug, and illegal versions of this medicine led to lethal incidents in the past. Therefore, it is crucial for the public health sector to develop reliable, efficient, cheap, unbiased and easily applicable active pharmaceutical ingredient (API) identification and quantification strategies for routine analysis of suspected illegal insulins. Here we demonstrate that our combined label-free full scan approach is not only able to distinguish between all those different versions of insulin and the insulins originating from different species, but also able to chromatographically separate human insulin and insulin lispro in conditions that are compatible with mass spectrometry (MS). Additionally, we were also able to selectively quantify the different insulins, including human insulin and insulin lispro according to the validation criteria, put forward by the United Nations (UN), for the analysis of seized illicit drugs. The proposed identification and quantification method is currently being used in our official medicines control laboratory to analyze insulins retrieved from the illegal market.

VL - 6 CP - 5 U1 - 2538 M3 - 10.1016/j.jpha.2016.04.006 ER - TY - JOUR T1 - Testing of complementarity of PDA and MS detectors using chromatographic fingerprinting of genuine and counterfeit samples containing sildenafil citrate. JF - Anal Bioanal Chem Y1 - 2016 A1 - Custers, Deborah A1 - Krakowska, Barbara A1 - De Beer, Jacques O A1 - Patricia Courselle A1 - Daszykowski, Michal A1 - Apers, Sandra A1 - Eric Deconinck KW - Chromatography, High Pressure Liquid KW - Counterfeit Drugs KW - Mass Spectrometry KW - Principal Component Analysis KW - Sensitivity and Specificity KW - Signal Processing, Computer-Assisted KW - Sildenafil Citrate AB -

Counterfeit medicines are a global threat to public health. High amounts enter the European market, which is why characterization of these products is a very important issue. In this study, a high-performance liquid chromatography-photodiode array (HPLC-PDA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) method were developed for the analysis of genuine Viagra®, generic products of Viagra®, and counterfeit samples in order to obtain different types of fingerprints. These data were included in the chemometric data analysis, aiming to test whether PDA and MS are complementary detection techniques. The MS data comprise both MS1 and MS2 fingerprints; the PDA data consist of fingerprints measured at three different wavelengths, i.e., 254, 270, and 290 nm, and all possible combinations of these wavelengths. First, it was verified if both groups of fingerprints can discriminate between genuine, generic, and counterfeit medicines separately; next, it was studied if the obtained results could be ameliorated by combining both fingerprint types. This data analysis showed that MS1 does not provide suitable classification models since several genuines and generics are classified as counterfeits and vice versa. However, when analyzing the MS1_MS2 data in combination with partial least squares-discriminant analysis (PLS-DA), a perfect discrimination was obtained. When only using data measured at 254 nm, good classification models can be obtained by k nearest neighbors (kNN) and soft independent modelling of class analogy (SIMCA), which might be interesting for the characterization of counterfeit drugs in developing countries. However, in general, the combination of PDA and MS data (254 nm_MS1) is preferred due to less classification errors between the genuines/generics and counterfeits compared to PDA and MS data separately.

VL - 408 CP - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26753972?dopt=Abstract M3 - 10.1007/s00216-015-9275-0 ER - TY - JOUR T1 - Analysis of illegal peptide biopharmaceuticals frequently encountered by controlling agencies. JF - Talanta Y1 - 2015 A1 - Celine Vanhee A1 - Steven Janvier A1 - Bart Desmedt A1 - Moens, Goedele A1 - Eric Deconinck A1 - De Beer, Jacques O A1 - Patricia Courselle KW - Belgium KW - Chromatography, Liquid KW - Counterfeit Drugs KW - Government Agencies KW - Peptides KW - Tandem Mass Spectrometry AB -

Recent advances in genomics, recombinant expression technologies and peptide synthesis have led to an increased development of protein and peptide therapeutics. Unfortunately this goes hand in hand with a growing market of counterfeit and illegal biopharmaceuticals, including substances that are still under pre-clinical and clinical development. These counterfeit and illegal protein and peptide substances could imply severe health threats as has been demonstrated by numerous case reports. The Belgian Federal Agency for Medicines and Health Products (FAMHP) and customs are striving, together with their global counterparts, to curtail the trafficking and distributions of these substances. At their request, suspected protein and peptide preparations are analysed in our Official Medicines Control Laboratory (OMCL). It stands to reason that a general screening method would be beneficiary in the battle against counterfeit and illegal peptide drugs. In this paper we present such general screening method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the identification of counterfeit and illegal injectable peptide preparations, extended with a subsequent quantification method using ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD). The screening method, taking only 30 min, is able to selectively detect 25 different peptides and incorporates the proposed minimum of five identification points (IP) as has been recommended for sports drug testing applications. The group of peptides represent substances which have already been detected in illegal and counterfeit products seized by different European countries as well as some biopharmaceutical peptides which have not been confiscated yet by the controlling agencies, but are already being used according to the many internet users forums. Additionally, we also show that when applying the same LC gradient, it is also possible to quantify these peptides without the need for derivatization or the use of expensive labelled peptides. This quantification method was successfully validated for a representative subset of 10 different peptides by using the "total error" approach in accordance with the validation requirements of ISO-17025.

VL - 142 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26003685?dopt=Abstract M3 - 10.1016/j.talanta.2015.04.022 ER - TY - JOUR T1 - ATR-FTIR spectroscopy and chemometrics: An interesting tool to discriminate and characterize counterfeit medicines. JF - J Pharm Biomed Anal Y1 - 2015 A1 - Custers, D A1 - Cauwenbergh, T A1 - Bothy, J L A1 - Patricia Courselle A1 - De Beer, J O A1 - Apers, S A1 - Eric Deconinck KW - Counterfeit Drugs KW - Principal Component Analysis KW - Spectroscopy, Fourier Transform Infrared AB -

Counterfeit medicines pose a huge threat to public health worldwide. High amounts of counterfeit pharmaceuticals enter the European market and therefore detection of these products is essential. Attenuated Total Reflection Fourier-Transform infrared spectroscopy (ATR-FTIR) might be useful for the screening of counterfeit medicines since it is easy to use and little sample preparation is required. Furthermore, this approach might be helpful to customs to obtain a first evaluation of suspected samples. This study proposes a combination of ATR-FTIR and chemometrics to discriminate and classify counterfeit medicines. A sample set, containing 209 samples in total, was analyzed using ATR-FTIR and the obtained spectra were used as fingerprints in the chemometric data-analysis which included Principal Component Analysis (PCA), k-Nearest Neighbours (k-NN), Classification and Regression Trees (CART) and Soft Independent Modelling of Class Analogy (SIMCA). First it was verified whether the mentioned techniques are capable to distinguish samples containing different active pharmaceutical ingredients (APIs). PCA showed a clear tendency of discrimination based on the API present; k-NN, CART and SIMCA were capable to create suitable prediction models based on the presence of different APIs. However k-NN performs the least while SIMCA performs the best. Secondly, it was tested whether these three models could be expanded to discriminate between genuine and counterfeit samples as well. k-NN was not able to make the desired discrimination and therefore it was not useful. CART performed better but also this model was less suited. SIMCA, on the other hand, resulted in a model with a 100% correct discrimination between genuine and counterfeit drugs. This study shows that chemometric analysis of ATR-FTIR fingerprints is a valuable tool to discriminate genuine from counterfeit samples and to classify counterfeit medicines.

VL - 112 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25476739?dopt=Abstract M3 - 10.1016/j.jpba.2014.11.007 ER - TY - JOUR T1 - Development of a Stationary Phase Optimised Selectivity Liquid Chromatography based screening method for adulterations of food supplements for the treatment of pain. JF - Talanta Y1 - 2015 A1 - Eric Deconinck A1 - Angelique Kamugisha A1 - Van Campenhout, P A1 - Patricia Courselle A1 - De Beer, J O KW - Chromatography, Liquid KW - Dietary Supplements KW - Drug Contamination KW - Humans KW - Hydrophobic and Hydrophilic Interactions KW - pain KW - Pesticide residues KW - Plant Preparations KW - Tandem Mass Spectrometry AB -

Illegally adulterated dietary supplements are an increasing problem worldwide. One of the important groups of often adulterated products are the dietary supplements, sold for the treatment of pain. These often contain analgesics, a heterogeneous group of molecules, containing both hydrophilic and hydrophobic compounds. The development of a screening method for these components, especially when mass spectrometric detection is not available, necessitates chromatographic separation, difficult to achieve with traditional chromatographic columns. In this paper Stationary Phase Optimised Selectivity Liquid Chromatography was used for the development of a screening method for nine analgesics, codeine and caffeine, often present in this type of dietary supplements. The method shows a good separation of all the compounds, allowing the screening to be performed with diode array detection and is fully compatible with mass spectrometry. The method was validated for its selectivity following the guidelines as described for the screening of pesticide residues and residues of veterinary medicines in food.

VL - 138 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25863397?dopt=Abstract M3 - 10.1016/j.talanta.2015.03.010 ER - TY - JOUR T1 - HS-GC-MS method for the analysis of fragrance allergens in complex cosmetic matrices. JF - Talanta Y1 - 2015 A1 - Bart Desmedt A1 - Michael Canfyn A1 - Pype, M A1 - S. Baudewyns A1 - Hanot, V A1 - Patricia Courselle A1 - De Beer, J O A1 - Rogiers, V A1 - De Paepe, K A1 - Eric Deconinck KW - Allergens KW - Cosmetics KW - Gas Chromatography-Mass Spectrometry KW - Humans KW - Odorants KW - Perfume KW - SKIN AB -

Potential allergenic fragrances are part of the Cosmetic Regulation with labelling and concentration restrictions. This means that they have to be declared on the ingredients list, when their concentration exceeds the labelling limit of 10 ppm or 100 ppm for leave-on or rinse-off cosmetics, respectively. Labelling is important regarding consumer safety. In this way, sensitised people towards fragrances might select their products based on the ingredients list to prevent elicitation of an allergic reaction. It is therefore important to quantify potential allergenic ingredients in cosmetic products. An easy to perform liquid extraction was developed, combined with a new headspace GC-MS method. The latter was capable of analysing 24 volatile allergenic fragrances in complex cosmetic formulations, such as hydrophilic (O/W) and lipophilic (W/O) creams, lotions and gels. This method was successfully validated using the total error approach. The trueness deviations for all components were smaller than 8%, and the expectation tolerance limits did not exceed the acceptance limits of ± 20% at the labelling limit. The current methodology was used to analyse 18 cosmetic samples that were already identified as being illegal on the EU market for containing forbidden skin whitening substances. Our results showed that these cosmetic products also contained undeclared fragrances above the limit value for labelling, which imposes an additional health risk for the consumer.

VL - 131 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25281125?dopt=Abstract M3 - 10.1016/j.talanta.2014.08.006 ER - TY - JOUR T1 - Identification of (antioxidative) plants in herbal pharmaceutical preparations and dietary supplements. JF - Methods Mol Biol Y1 - 2015 A1 - Eric Deconinck A1 - Custers, Deborah A1 - De Beer, Jacques Omer KW - Acetonitriles KW - Antioxidants KW - Dietary Supplements KW - Hydrogen-Ion Concentration KW - Mass Spectrometry KW - Methanol KW - Passiflora KW - Pharmaceutical Preparations KW - Plant Preparations KW - Reproducibility of Results KW - Solvents AB -

The standard procedures for the identification, authentication, and quality control of medicinal plants and herbs are nowadays limited to pure herbal products. No guidelines or procedures, describing the detection or identification of a targeted plant or herb in pharmaceutical preparations or dietary supplements, can be found. In these products the targeted plant is often present together with other components of herbal or synthetic origin. This chapter describes a strategy for the fast development of a chromatographic fingerprint approach that allows the identification of a targeted plant in herbal preparations and dietary supplements. The strategy consists of a standard chromatographic gradient that is tested for the targeted plant with different extraction solvents and different mobile phases. From the results obtained, the optimal fingerprint is selected. Subsequently the samples are analyzed according to the selected methodological parameters, and the obtained fingerprints can be compared with the one obtained for the pure herbal product or a standard preparation. Calculation of the dissimilarity between these fingerprints will result in a probability of presence of the targeted plant. Optionally mass spectrometry can be used to improve specificity, to confirm identification, or to identify molecules with a potential medicinal or antioxidant activity.

VL - 1208 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25323508?dopt=Abstract M3 - 10.1007/978-1-4939-1441-8_14 ER - TY - JOUR T1 - Identification of the small research tetra peptide Epitalon, assumed to be a potential treatment for cancer, old age and Retinitis Pigmentosa in two illegal pharmaceutical preparations. JF - Drug Test Anal Y1 - 2015 A1 - Celine Vanhee A1 - Moens, Goedele A1 - Els Van Hoeck A1 - Eric Deconinck A1 - De Beer, Jacques O KW - Aging KW - Antineoplastic Agents KW - Chromatography, Liquid KW - Humans KW - Mass Spectrometry KW - Neoplasms KW - Oligopeptides KW - Retinitis Pigmentosa KW - Street Drugs VL - 7 CP - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25535022?dopt=Abstract M3 - 10.1002/dta.1771 ER - TY - THES T1 - Illegal cosmetics on the Belgian market Y1 - 2015 A1 - Bart Desmedt A1 - Eric Deconinck A1 - De Beer, Jacques O A1 - Patricia Courselle A1 - K De Paepe A1 - V Rogiers KW - Cosmetics KW - dermal absorption KW - skin whitening PB - VUB CY - Brussels, Belgium ER - TY - JOUR T1 - In vitro Dermal Absorption: Sample Application and Seal Quality in a Franz Diffusion Cell System. JF - Skin Pharmacol Physiol Y1 - 2015 A1 - Bart Desmedt A1 - Patricia Courselle A1 - De Beer, Jacques O A1 - Rogiers, Vera A1 - Eric Deconinck A1 - De Paepe, Kristien KW - Administration, Cutaneous KW - Densitometry KW - Diffusion KW - Diffusion Chambers, Culture KW - Humans KW - In Vitro Techniques KW - SKIN KW - Skin Absorption KW - Temperature AB -

One of the known drawbacks of in vitro dermal absorption methods is their high interlaboratory variation. Although often attributed to biological skin differences, it has been shown that validation of other parameters such as temperature and stirring speed can reduce the high variability observed. The Organisation for Economic Co-operation and Development (OECD) and, at the EU level, the Scientific Committee on Consumer Safety (SCCS) have published guidance documents of how to perform these in vitro tests. For the parameter 'sample application' and 'adequate seal', it is indicated to apply the sample homogeneously and provide an adequate seal between the donor chamber and the membrane on which the sample is applied. Here, a simple and visual densitometer-based method is provided, which makes evaluation possible of any application protocol used.

VL - 28 CP - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25765467?dopt=Abstract M3 - 10.1159/000375321 ER - TY - JOUR T1 - Occurrence of volatile organic compounds in foods from the Belgian market and dietary exposure assessment JF - Food Control Y1 - 2015 A1 - R. Medeiros Vinci A1 - Jacxsens,L. A1 - De Meulenaer,B. A1 - Eric Deconinck A1 - E. Matsiko A1 - Lachat,C. A1 - De Schaetzen,T. A1 - Michael Canfyn A1 - Ilse Van Overmeire A1 - Kolsteren,P. A1 - Joris Van Loco KW - Adult KW - Adult-population KW - Belgian KW - benzene KW - chronic KW - daily intake KW - Diet KW - dietary KW - Dietary exposure KW - Dietary intake KW - Dietary-intake KW - environment KW - exposure KW - food KW - Foods KW - health KW - identify KW - intake KW - IS KW - IT KW - LEVEL KW - occurrence KW - Order KW - organic KW - POPULATION KW - present KW - risk KW - risks KW - Sample KW - Samples KW - study AB - Because volatile organic compounds (VOCs) are ubiquitous in the environment and may represent health risks, it is important to know whether they are present in our diet and to identify possible sources in order to reduce daily intake. In the present study, 377 food samples from the Belgian market were screened for the presence of 21 VOCs. The most prevalent of these compounds and respective percentages of occurrence were: chloroform (97%), toluene (95%), ethyl benzene (80%), o-xylene (79%) and benzene (58%). Dietary intake by the Belgian adult population was calculated for these five most prevalent VOCs. The maximum probabilistic dietary intake was with 0.151, 0.645, 0.138, 0.066 and 0.118 µg kg bw VL - 52 U1 - 2332 M3 - http://dx.doi.org/doi:10.1016/j.foodcont.2014.12.010 ER - TY - Generic T1 - ANALYSIS OF COUNTERFEIT BIOPHARMACEUTICALS SEIZED BY THE BELGIAN AUTHORITIES Y1 - 2014 A1 - Celine Vanhee ED - Goedele Moens KW - Illegal biopharmaceuticals PB - Drug analysis and PBA 2014 CY - Liege ER - TY - Generic T1 - Analysis of counterfeit biopharmaceuticals seized by the Belgian authorities Y1 - 2014 A1 - Celine Vanhee A1 - G.F. Moens A1 - Eric Deconinck A1 - J. De Beer KW - abstract KW - analysi KW - analysis KW - Belgian KW - Counterfeit KW - Medicine KW - medicines KW - symposium AB -

No abstract available

JF - Combating counterfeit and other illegal medicines: symposium for OMCLs PB - NA CY - NA CP - EDQM U1 - 2279 U2 - 10-11/09/2014 ER - TY - Generic T1 - Attenuated Total Reflection-Infrared Spectroscopy: an interesting tool to classify counterfeit medicines? Y1 - 2014 A1 - Custers,D. A1 - Patricia Courselle A1 - J. De Beer A1 - Apers,S. A1 - Eric Deconinck KW - an KW - analysi KW - analysis KW - Counterfeit KW - Counterfeit medicines KW - DRUG KW - Medicine KW - medicines JF - Drug Analysis 2014 PB - NA CY - NA CP - PBA U1 - 2276 U2 - 22-25 June 2014 ER - TY - JOUR T1 - Characterization of suspected illegal skin whitening cosmetics. JF - J Pharm Biomed Anal Y1 - 2014 A1 - Bart Desmedt A1 - Els Van Hoeck A1 - Rogiers, V A1 - Patricia Courselle A1 - De Beer, J O A1 - De Paepe, K A1 - Eric Deconinck KW - Belgium KW - Chromatography, High Pressure Liquid KW - Clobetasol KW - Cosmetics KW - Dermatologic Agents KW - European Union KW - Glucocorticoids KW - Humans KW - Hydroquinones KW - Legislation, Drug KW - Mass Spectrometry KW - Skin Lightening Preparations KW - tretinoin AB -

An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin.

VL - 90 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24334193?dopt=Abstract M3 - 10.1016/j.jpba.2013.11.024 ER - TY - JOUR T1 - Comparative dissolution study on counterfeit medicines of PDE-5 inhibitors JF - Journal of Pharmaceutical Analysis Y1 - 2014 A1 - Eric Deconinck A1 - Andriessens,S. A1 - Bothy,J.L. A1 - Patricia Courselle A1 - J. De Beer KW - abstract KW - AS KW - at KW - Cochran test KW - Comparison KW - Counterfeit KW - Counterfeit medicines KW - Countries KW - developing KW - EVALUATION KW - f2-Method KW - general KW - identification KW - In vitro dissolution KW - IS KW - Medicine KW - medicines KW - ON KW - PDE-5 inhibitors KW - PRODUCTS KW - profile KW - Profiles KW - result KW - results KW - study KW - Test KW - tests KW - time KW - variation KW - variations AB - Abstract Counterfeit medicines are a growing problem in both developing and industrialised countries. In general the evaluation of these medicines is limited to the identification and the dosage of the active ingredients. In this study in vitro dissolution tests were conducted on two sets of counterfeit medicines containing PDE-5 inhibitors (sildenafil citrate and tadalafil). The dissolution profiles were statistically compared to the ones of the genuine products using the f2-method and a comparison at each time point using the Cochran test. The results showed low equivalences between counterfeit and genuine products as well as higher variations around the mean dissolution value at the different time points for the counterfeit products VL - 4 SN - 2095-1779 CP - 4 U1 - 2259 M3 - http://dx.doi.org/10.1016/j.jpha.2014.03.002 ER - TY - Generic T1 - Des produits de blanchiment de la peau illégaux toujours présents sur le marché belge Y1 - 2014 A1 - Eric Deconinck KW - de KW - LE KW - produits de blanchiment U1 - 2336 ER - TY - JOUR T1 - Detection of sibutramine in adulterated dietary supplements using attenuated total reflectance-infrared spectroscopy. JF - J Pharm Biomed Anal Y1 - 2014 A1 - Eric Deconinck A1 - Cauwenbergh, T A1 - Bothy, J L A1 - Custers, D A1 - Patricia Courselle A1 - De Beer, J O KW - Appetite Depressants KW - Cyclobutanes KW - Decision Trees KW - Dietary Supplements KW - Drug Contamination KW - False Positive Reactions KW - Least-Squares Analysis KW - Principal Component Analysis KW - Reproducibility of Results KW - Spectrophotometry, Infrared AB -

Sibutramine is one of the most occurring adulterants encountered in dietary supplements with slimming as indication. These adulterated dietary supplements often contain a herbal matrix. When customs intercept these kind of supplements it is almost impossible to discriminate between the legal products and the adulterated ones, due to misleading packaging. Therefore in most cases these products are confiscated and send to laboratories for analysis. This results inherently in the confiscation of legal, non-adulterated products. Therefore there is a need for easy to use equipment and techniques to perform an initial screening of samples. Attenuated total reflectance-infrared (ATR-IR) spectroscopy was evaluated for the detection of sibutramine in adulterated dietary supplements. Data interpretation was performed using different basic chemometric techniques. It was found that the use of ATR-IR combined with the k-Nearest Neighbours (k-NN) was able to detect all adulterated dietary supplements in an external test set and this with a minimum of false positive results. This means that a small amount of legal products will still be confiscated and analyzed in a laboratory to be found negative, but no adulterated samples will pass the initial ATR-IR screening.

VL - 100 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25173110?dopt=Abstract M3 - 10.1016/j.jpba.2014.08.009 ER - TY - Generic T1 - Detection of whitening agents in illegal cosmetics using attenuated total reflectance-infrared spectroscopy Y1 - 2014 A1 - Eric Deconinck A1 - Bothy,J.L. A1 - B. De Smet A1 - Patricia Courselle A1 - J. De Beer KW - Agent KW - Agents KW - analysi KW - analysis KW - cosmetic KW - Cosmetics KW - detection KW - DRUG KW - illegal cosmetics KW - whitening JF - Drug analysis 2014 PB - NA CY - NA CP - BGFW U1 - 2254 U2 - 23-25 june 2014 ER - TY - JOUR T1 - Detection of whitening agents in illegal cosmetics using attenuated total reflectance-infrared spectroscopy. JF - J Pharm Biomed Anal Y1 - 2014 A1 - Eric Deconinck A1 - Bothy, J L A1 - Bart Desmedt A1 - Patricia Courselle A1 - De Beer, J O KW - Bleaching Agents KW - Cosmetics KW - Principal Component Analysis KW - Spectrophotometry, Infrared AB -

Cosmetic products containing illegal whitening agents are still found on the European market. They represent a considerable risk to public health, since they are often characterised by severe side effects when used chronically. The detection of such products at customs is not always simple, due to misleading packaging and the existence of products containing only legal components. Therefore there is a need for easy to use equipment and techniques to perform an initial screening of samples. The use of attenuated total reflectance-infrared (ATR-IR) spectroscopy, combined with chemometrics, was evaluated for that purpose. It was found that the combination of ATR-IR with the simple chemometric technique k-nearest neighbours gave good results. A model was obtained in which a minimum of illegal samples was categorised as legal. The correctly classified illegal samples could be attributed to the illegal components present.

VL - 98 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24927403?dopt=Abstract M3 - 10.1016/j.jpba.2014.05.011 ER - TY - JOUR T1 - Headspace-gas chromatographic fingerprints to discriminate and classify counterfeit medicines. JF - Talanta Y1 - 2014 A1 - Custers, D A1 - Michael Canfyn A1 - Patricia Courselle A1 - De Beer, J O A1 - Apers, S A1 - Eric Deconinck KW - Carbolines KW - Counterfeit Drugs KW - Drug Contamination KW - Gas Chromatography-Mass Spectrometry KW - Piperazines KW - Principal Component Analysis KW - Purines KW - Reproducibility of Results KW - Risk Factors KW - Sildenafil Citrate KW - Sulfonamides KW - Tadalafil AB -

Counterfeit medicines are a global threat to public health. These pharmaceuticals are not subjected to quality control and therefore their safety, quality and efficacy cannot be guaranteed. Today, the safety evaluation of counterfeit medicines is mainly based on the identification and quantification of the active substances present. However, the analysis of potential toxic secondary components, like residual solvents, becomes more important. Assessment of residual solvent content and chemometric analysis of fingerprints might be useful in the discrimination between genuine and counterfeit pharmaceuticals. Moreover, the fingerprint approach might also contribute in the evaluation of the health risks different types of counterfeit medicines pose. In this study a number of genuine and counterfeit Viagra(®) and Cialis(®) samples were analyzed for residual solvent content using headspace-GC-MS. The obtained chromatograms were used as fingerprints and analyzed using different chemometric techniques: Principal Component Analysis, Projection Pursuit, Classification and Regression Trees and Soft Independent Modelling of Class Analogy. It was tested whether these techniques can distinguish genuine pharmaceuticals from counterfeit ones and if distinct types of counterfeits could be differentiated based on health risks. This chemometric analysis showed that for both data sets PCA clearly discriminated between genuine and counterfeit drugs, and SIMCA generated the best predictive models. This technique not only resulted in a 100% correct classification rate for the discrimination between genuine and counterfeit medicines, the classification of the counterfeit samples was also superior compared to CART. This study shows that chemometric analysis of headspace-GC impurity fingerprints allows to distinguish between genuine and counterfeit medicines and to differentiate between groups of counterfeit products based on the public health risks they pose.

VL - 123 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24725867?dopt=Abstract M3 - 10.1016/j.talanta.2014.01.020 ER - TY - Generic T1 - How to improve the high variability of the in vitro dermal absorption test Y1 - 2014 A1 - B. De Smet A1 - Patricia Courselle A1 - J. De Beer A1 - V Rogiers A1 - Eric Deconinck A1 - De Paepe,K. ED - National Institute of Public Health KW - alternatives KW - Animal KW - Congresses KW - dermal absorption KW - improve KW - Life KW - ON KW - Science KW - Test KW - use KW - VARIABILITY KW - world JF - 9th world congress on alternatives fand animal use in the life sciences CP - national institute of pubic health U1 - 2282 U2 - 24-28/08/2014 ER - TY - JOUR T1 - Identification and characterization of peptide drugs in unknown pharmaceutical preparations seized by the Belgian authorities: case report on AOD9604. JF - Drug Test Anal Y1 - 2014 A1 - Celine Vanhee A1 - Moens, Goedele A1 - Eric Deconinck A1 - De Beer, Jacques O KW - Belgium KW - Chromatography, Liquid KW - Counterfeit Drugs KW - Drug and Narcotic Control KW - Electrophoresis, Polyacrylamide Gel KW - Peptide Fragments KW - Peptides KW - Pharmaceutical Preparations KW - Somatostatin KW - Tandem Mass Spectrometry VL - 6 CP - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24976118?dopt=Abstract M3 - 10.1002/dta.1687 ER - TY - BOOK T1 - Identification of (anti-oxidative) plants in herbal pharmaceutical preparations and dietary supplements T2 - Advanced Protocols in Oxidative Stress-III Y1 - 2014 A1 - Eric Deconinck A1 - Custers,D. A1 - J.L. de Beer ED - D. Armastrong KW - dietary KW - identification KW - Pharmaceutical Preparations KW - plant KW - Plants KW - protocol JF - Advanced Protocols in Oxidative Stress-III PB - Springer CY - NA SN - NA U1 - 2217 ER - TY - JOUR T1 - Illegal cosmetics on the EU market: a threat for human health? JF - Arch Toxicol Y1 - 2014 A1 - Bart Desmedt A1 - Patricia Courselle A1 - De Beer, J O A1 - Rogiers, V A1 - Eric Deconinck A1 - De Paepe, K KW - Belgium KW - Consumer Product Safety KW - Cosmetics KW - Crime KW - Dermatitis, Allergic Contact KW - European Union KW - Humans KW - Product Labeling KW - Skin Lightening Preparations VL - 88 CP - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25079448?dopt=Abstract M3 - 10.1007/s00204-014-1317-4 ER - TY - Generic T1 - Illegal medicines: a challenge for analytical chemists, a treat for public health Y1 - 2014 A1 - Eric Deconinck ED - Svenska Kemiportalen KW - challenge KW - health KW - Medicine KW - medicines KW - public KW - public health KW - Public-health KW - Treat JF - Analysisdagarana 2014 CP - Svenska Kemiportalen. U1 - 2252 U2 - 9-11/06/2014 ER - TY - Generic T1 - Illegale huidbleekmiddelen nog steeds op Belgische markt Y1 - 2014 A1 - Eric Deconinck KW - Belgische KW - huidbleekmiddelen U1 - 2335 ER - TY - Generic T1 - Residual Solvents: A potential threat present in counterfeit medicines Y1 - 2014 A1 - Eric Deconinck A1 - Michael Canfyn A1 - J.L. de Beer KW - analysi KW - analysis KW - DRUG KW - present KW - Solvents JF - Drug Analysis 2014 PB - NA CY - NA CP - BGFW, BGFW U1 - 2253 U2 - 23-25/06/2014 ER - TY - BOOK T1 - Residual solvents in pharmaceutical substances and products T2 - Handbook of Solvents-2nd edition Y1 - 2014 A1 - Eric Deconinck A1 - J.L. de Beer ED - Wypych,G. KW - PRODUCTS KW - Solvents JF - Handbook of Solvents-2nd edition PB - Chemtec Publishing CY - Toronto VL - 2 Use, health and environment SN - 978-1-895198-65-2 U1 - 2218 ER - TY - Generic T1 - Undeclared allergenic fragrances in cosmetics Y1 - 2014 A1 - B. De Smet A1 - Michael Canfyn A1 - Patricia Courselle A1 - J. De Beer A1 - V Rogiers A1 - De Paepe,K. A1 - Eric Deconinck KW - allergenic KW - analysi KW - analysis KW - DRUG KW - fragrances JF - Drug Analysis 2014 PB - NA CY - NA CP - BGFW U1 - 2281 U2 - 21-25/06/2014 ER - TY - Generic T1 - Chromatographic fingerprints to discriminate counterfeit medicines and characterize illegal pharmaceutical preparations. Y1 - 2013 A1 - Eric Deconinck A1 - Patricia Courselle A1 - J.L. de Beer KW - analysi KW - analysis KW - Chromatographic fingerprints KW - Counterfeit medicines KW - Medicine KW - Pharmaceutical Preparations JF - Pharmaceutical and Biomedical analysis 2013 PB - NA CY - NA CP - European Federation for medicinal chemistry U1 - 2135 U2 - 30/06/2013-04/07/2013 ER - TY - JOUR T1 - Chromatography in the detection and characterization of illegal pharmaceutical preparations. JF - J Chromatogr Sci Y1 - 2013 A1 - Eric Deconinck A1 - Sacré, Pierre-Yves A1 - Patricia Courselle A1 - De Beer, Jacques O KW - chromatography KW - Counterfeit Drugs KW - Street Drugs KW - Substance Abuse Detection AB -

Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques such as infrared spectroscopy and Raman spectroscopy have always been the first methods of choice to detect counterfeits and illegal preparations, but due to the evolution in the seized products and the necessity of risk assessment, chromatographic methods are becoming more important in this domain. This review intends to give a general overview of the techniques described in literature to characterize counterfeit and illegal pharmaceutical preparations, focusing on the role of chromatographic techniques with different detection tools.

VL - 51 CP - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23377647?dopt=Abstract M3 - 10.1093/chromsci/bmt006 ER - TY - Generic T1 - Classification trees based on infrared spectroscopic data to discriminate between genuine and counterfeit medicines Y1 - 2013 A1 - Eric Deconinck A1 - P.Y. Sacré A1 - J. De Beer KW - analysi KW - analysis KW - classification KW - data KW - ON KW - trees JF - Recent Devloment in Pharmaceutical Analysis 2011 PB - NA CY - NA CP - Italian pharmaceutical society U1 - 2134 U2 - 21-24/09/2011 ER - TY - Generic T1 - Determination of steviol glycosides Rebaudioside A in soft drinks by RP-amide liquid chromatography Y1 - 2013 A1 - Van den Bergh,M. A1 - Eric Deconinck A1 - Séverine Goscinny A1 - Joris Van Loco ED - Marie-Louise Scippo KW - alimentation KW - an KW - AS KW - at KW - chromatography KW - Components KW - composition KW - consumer KW - CONTACT KW - Control KW - daily intake KW - de KW - diabetic KW - Diet KW - dietary KW - Dietary intake KW - Dietary-intake KW - drinks KW - EU KW - FNRS KW - food KW - glycosides KW - intake KW - IS KW - liquid chromatography KW - measure KW - method KW - methods KW - NUTRITION KW - plant KW - regulation KW - SAFETY KW - santé KW - study KW - symposium KW - Taste KW - work AB - The additive steviol glycosides (E960) is a plant (Stevia Rebaudiana Bertoni) extract that contains at least 95% of seven steviol glycosides but there are four dominant components: stevioside, rebaudioside A and C, dulcoside A. Rebaudioside A (Reb A) JF - Septième symposium du Groupe de Contact FNRS Nutrition, Alimentation et Santé GCNAS T3 - Groupe de contact FNRS GNCAS CP - Scippo,M.L. U1 - 2225 U2 - 6/12/2013 ER - TY - JOUR T1 - Development and validation of a fast chromatographic method for screening and quantification of legal and illegal skin whitening agents. JF - J Pharm Biomed Anal Y1 - 2013 A1 - Bart Desmedt A1 - Rogiers, V A1 - Patricia Courselle A1 - De Beer, J O A1 - De Paepe, K A1 - Eric Deconinck KW - Chromatography, High Pressure Liquid KW - Cosmetics KW - Dermatologic Agents KW - SKIN KW - Skin Lightening Preparations AB -

During the last years, the EU market is flooded by illegal cosmetics via the Internet and a so-called "black market". Among these, skin-bleaching products represent an important group. They contain, according to the current European cosmetic legislation (Directive 76/768/EEC), a number of illegal active substances including hydroquinone, tretinoin and corticosteroids. These may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. To control this market there is a need for a fast screening method capable of detecting illegal ingredients in the wide variety of existing bleaching cosmetic formulations. In this paper the development and validation of an ultra high pressure liquid chromatographic (UHPLC) method is described. The proposed method makes use of a Waters Acquity BEH shield RP18 column with a gradient using 25 mM ammonium borate buffer (pH 10) and acetonitrile. This method is not only able to detect the major illegal (hydroquinone, tretinoin and six dermatologic active corticosteroids) and legal whitening agents, the latter having restrictions with respect to concentration and application (kojic acid, arbutin, nicotinamide and salicylic acid), but can also quantify these in a run time of 12 min. The method was successfully validated using the "total error" approach in accordance with the validation requirements of ISO-17025. During the validation a variety of cosmetic matrices including creams, lotions and soaps were taken into consideration.

VL - 83 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23708434?dopt=Abstract M3 - 10.1016/j.jpba.2013.04.020 ER - TY - THES T1 - Evaluatie van de Bioequivalentie van counterfeit geneesmiddelen aan de hand van dissolutieprofielen Y1 - 2013 A1 - Andriessens,S. A1 - Eric Deconinck KW - AAN KW - bioequivalentie KW - Counterfeit KW - Counterfeit Drugs KW - de KW - dissolutie KW - geneesmiddelen KW - Hand PB - VUB CY - Brussels U1 - 2162 ER - TY - JOUR T1 - Evaluation of the residual solvent content of counterfeit tablets and capsules. JF - J Pharm Biomed Anal Y1 - 2013 A1 - Eric Deconinck A1 - Michael Canfyn A1 - Sacré, P-Y A1 - Patricia Courselle A1 - De Beer, J O KW - Capsules KW - Carbolines KW - Counterfeit Drugs KW - Gas Chromatography-Mass Spectrometry KW - Guidelines as Topic KW - Phosphodiesterase 5 Inhibitors KW - Piperazines KW - Purines KW - Sildenafil Citrate KW - Solvents KW - Sulfones KW - Tablets KW - Tadalafil AB -

A group of counterfeit samples of Viagra and Cialis were screened for their residual solvent content and compared to the content of the genuine products. It was observed that all counterfeit samples had higher residual solvent contents compared to the genuine products. A more diverse range of residual solvents was found as well as higher concentrations. In general these concentrations did not exceed the international imposed maximum limits. Only in a few samples the limits were exceeded. A Projection Pursuit analysis revealed clusters of samples with similar residual solvent content, possibly enabling some future perspectives in forensic research.

VL - 81-82 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23628524?dopt=Abstract M3 - 10.1016/j.jpba.2013.03.023 ER - TY - Generic T1 - Headspace-gas chromatoghraphic fingerprints to discriminate and classify counterfeit medicines Y1 - 2013 A1 - Custers,D. A1 - Patricia Courselle A1 - J.L. de Beer A1 - Apers,S. A1 - Eric Deconinck KW - Counterfeit medicines KW - Medicine KW - Science JF - 17th forum of pharmaceutical sciences PB - NA CY - NA CP - BGFW U1 - 2161 U2 - 17-18/10/2013 ER - TY - Generic T1 - Illegale huidblekende cosmetica op de Belgischemarkt (Des cosmétiques dépigmentants illégaux sur le marché belge) Y1 - 2013 A1 - B. De Smet A1 - V Rogiers A1 - Patricia Courselle A1 - J. De Beer A1 - De Paepe,K. A1 - Eric Deconinck KW - corticosteroids KW - cosmetica KW - de KW - Development KW - EU KW - gevaar KW - hydroquinone KW - illegal cosmetics KW - Internet KW - IS KW - LE KW - method KW - Salicylic Acid KW - study AB - Naast namaakgeneesmiddelen die de Europese markt overspoelen, is er ook een steeds groeiend probleem met illegale cosmetica. Huidbleekmiddelen vormen hierbij een belangrijke groep. Het zijn producten die topisch worden aangebracht, meestal op het gezicht, de handen en het decolleté om depigmentatie van de huid te bekomen. Ondanks de talrijke studies die duidelijk wijzen op ongewenste effecten en gevaar voor de volksgezondheid en het EU-verbod voor het gebruik van een aantal actieve substanties in cosmetica, blijft het gebruik ervan toenemen, vooral bij consumenten met fototype IV, V of VI. De verkoop van dergelijke producten gebeurt in Europa voornamelijk via de zwarte markt, etnisch cosmetische winkels en het internet. Gestimuleerd door een gezamenlijk onderzoeksproject tussen het Wetenschappelijk Instituut Volksgezondheid (WIVISP) en de Vrije Universiteit Brussel (VUB) werd een nieuwe methode ontwikkeld voor de analyse van verdachte huidblekende cosmetica. Vervolgens werd een marktonderzoek uitgevoerd gebaseerd op 161 in beslag genomen stalen. Uit de resultaten blijkt dat de verdachte stalen voornamelijk clobetasolpropionaat (een sterk werkzaam corticosteroïde), hydrochinon en tretinoïne bevatten als actieve bestanddelen. Deze ingrediënten zijn verboden in cosmetica in de EU en hebben specifieke bijwerkingen. Bij langdurig gebruik of overmatige blootstelling vormen ze een potentieel gevaar voor de consument. JF - skin VL - 16 U1 - 2145 ER - TY - JOUR T1 - A strategy for the identification of plants in illegal pharmaceutical preparations and food supplements using chromatographic fingerprints JF - Anal.Bioanal.Chem. Y1 - 2013 A1 - Eric Deconinck A1 - De Leersnijder,C. A1 - Custers,D. A1 - Patricia Courselle A1 - J. De Beer KW - analysis KW - article KW - AS KW - Belgium KW - Brussels KW - Chromatographic fingerprints KW - Common KW - consumer KW - Counterfeit medicines KW - detection KW - electronic KW - Feasibility Studies KW - food KW - health KW - identification KW - im KW - Institute KW - IS KW - journal KW - Laboratories KW - Light KW - Mass KW - Mass Spectrometry KW - Medicine KW - ON KW - Pharmaceutical Preparations KW - plant KW - Plants KW - PRODUCTS KW - public KW - public health KW - Public-health KW - SAFETY KW - SB - IM KW - Strategies KW - Strategy KW - study KW - Type KW - use AB - The detection of regulated and forbidden herbs in pharmaceutical preparations and nutritional supplements is a growing problem for laboratories charged with the analysis of illegal pharmaceutical preparations and counterfeit medicines. This article presents a feasibility study of the use of chromatographic fingerprints for the detection of plants in pharmaceutical preparations. Fingerprints were developed for three non-regulated common herbal products-Rhamnus purshiana, Passiflora incarnata L. and Crataegus monogyna-and this was done by combining three different types of detection: diode-array detection, evaporative light scattering detection and mass spectrometry. It is shown that these plants could be detected in respective triturations of the dry extracts with lactose and three different herbal matrices as well as in commercial preparations purchased on the open market VL - 405 CP - 7 U1 - 2118 M3 - http://dx.doi.org/10.1007/s00216-012-6649-4 ER - TY - RPRT T1 - Bruikbaarheid van chromatografische fingerprints voor de identificatie van planten in illegale farmaceutische bereidingen Y1 - 2012 A1 - De Leersnijder,C. ED - Eric Deconinck ED - Sarre,S. KW - de PB - VUB CY - Jette, Belgium U1 - 33772 ER - TY - JOUR T1 - Chemometrics and chromatographic fingerprints to discriminate and classify counterfeit medicines containing PDE-5 inhibitors. JF - Talanta Y1 - 2012 A1 - Eric Deconinck A1 - Sacré, P Y A1 - Patricia Courselle A1 - De Beer, J O KW - chromatography KW - Cluster Analysis KW - Counterfeit Drugs KW - Informatics KW - Least-Squares Analysis KW - Phosphodiesterase 5 Inhibitors KW - Principal Component Analysis KW - Support Vector Machine AB -

Chromatographic fingerprints recorded for a set of genuine and counterfeit samples of Viagra(®) and Cialis(®) were evaluated for their use in the detection and classification of counterfeit samples of these groups of medicines. Therefore several exploratory chemometric techniques were applied to reveal structures in the data sets as well as differences among the samples. The focus was on the differentiation between genuine and counterfeit samples and on the differences between the samples of the different classes of counterfeits as defined by the Dutch National Institute for Public Health and the Environment (RIVM). In a second part the revealed differences between the samples were modelled to obtain a predictive model for both the differentiation between genuine and counterfeit samples as well as the classification of the counterfeit samples. The exploratory analysis clearly revealed differences in the data for the genuine and the counterfeit samples and with projection pursuit and hierarchical clustering differences among the different groups of counterfeits could be revealed, especially for the Viagra(®) data set. For both data sets predictive models were obtained with 100% correct classification rates for the differentiation between genuine and counterfeit medicines and high correct classification rates for the classification in the different classes of counterfeit medicines. For both data sets the best performing models were obtained with Least Square-Support Vector Machines (LS-SVM) and Soft Independent Modelling by Class Analogy (SIMCA).

VL - 100 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23141319?dopt=Abstract M3 - 10.1016/j.talanta.2012.08.029 ER - TY - JOUR T1 - Classification trees based on infrared spectroscopic data to discriminate between genuine and counterfeit medicines. JF - J Pharm Biomed Anal Y1 - 2012 A1 - Eric Deconinck A1 - Sacré, P Y A1 - Coomans, D A1 - De Beer, J KW - Algorithms KW - Counterfeit Drugs KW - Spectroscopy, Fourier Transform Infrared KW - Spectroscopy, Near-Infrared KW - Spectrum Analysis, Raman AB -

Classification trees built with the Classification And Regression Tree algorithm were evaluated for modelling infrared spectroscopic data in order to discriminate between genuine and counterfeit drug samples and to classify counterfeit samples in different classes following the RIVM classification system. Models were built for two data sets consisting of the Fourier Transformed Infrared spectra, the near infrared spectra and the Raman spectra for genuine and counterfeit samples of respectively Viagra(®) and Cialis(®). Easy interpretable models were obtained for both models. The models were validated for their descriptive and predictive properties. The predictive properties were evaluated using both cross validation as an external validation set. The obtained models for both data sets showed a 100% correct classification for the discrimination between genuine and counterfeit samples and 83.3% and 100% correct classification for the counterfeit samples for the Viagra(®) and the Cialis(®) data set respectively.

VL - 57 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21940132?dopt=Abstract M3 - 10.1016/j.jpba.2011.08.036 ER - TY - Generic T1 - Classification trees based on infrared spectroscopic data to discriminate between genuine and counterfeit medicines Y1 - 2012 A1 - Eric Deconinck A1 - P.Y. Sacré A1 - Coomans,D. A1 - J. De Beer KW - ALL KW - an KW - AS KW - chemistry KW - Class KW - classification KW - Common KW - Counterfeit Drugs KW - Countries KW - data KW - developing KW - differences KW - discrimination KW - DRUG KW - drugs KW - external KW - health KW - Internet KW - IS KW - Literature KW - method KW - methods KW - MODEL KW - models KW - ON KW - Order KW - public KW - public health KW - Public-health KW - regression KW - Sample KW - Samples KW - System KW - Technique KW - use KW - world AB -

Due to the extension of the internet, counterfeit drugs represent a growing threat for public health in the developing countries but also more and more in the industrial world. In literature several analytical techniques were applied in order to discriminate between genuine and counterfeit medecines. One thing all these techniques have in common is that they generate a huge amount of data, which is often difficult to interpret in order to see differences between the different samples and to determine the cause of the differences. The majority of the authors make use of explorative chemometric tools to visualise the differences in the data obtained for the different samples. Even if some of the applied methods could be able to give a model with predictive ability, only a few authors created a model able to predict if a sample is counterfeit or not. Classification trees built with the Classification And Regression Tree algorithm were evaluated for modelling infrared spectroscopic data in order to discriminate between genuine and counterfeit drug samples and to classify counterfeit samples in different classes following the RIVM classification system. Models were built for two data sets consisting of the Fourrier Transformed Infrared spectra, the Near Infrared spectra and the Raman spectra for genuine and counterfeit samples of respectively Viagra

JF - Chemometrics In Analytical Chemistry 2012 PB - NA CY - NA CP - Hungarian Chemometrics Society U1 - 1870 U2 - 25/06/2012-29/06/2012 ER - TY - Generic T1 - Comparison and combination of spectroscopic techniques for the detection of counterfeit medecines Y1 - 2012 A1 - P.Y. Sacré A1 - Eric Deconinck A1 - De Beer,T A1 - R. Van Cauwenberghe A1 - Patricia Courselle A1 - Chiap,P. A1 - Crommen,J. A1 - J.L. de Beer ED - Belgian Society of Pharmaceutical Sciences KW - analysis KW - Combination KW - Comparison KW - detection KW - DRUG KW - Technique JF - Drug Analysis 2010 CP - Belgian Society of Pharmaceutical Sciences U1 - 1873 U2 - 21-24/09/2010 ER - TY - Generic T1 - Detection of counterfeit Viagra by Raman microscopy imaging and multivariate analysis Y1 - 2012 A1 - P.Y. Sacré A1 - Eric Deconinck A1 - Saerens,L. A1 - De Beer,T A1 - Patricia Courselle A1 - R. Van Cauwenberghe A1 - Chiap,P A1 - Crommen,J. A1 - J.L. de Beer KW - analysis KW - detection KW - Multivariate KW - Multivariate Analysis KW - Viagra JF - Combating Counterfeit and Other Illegal Medicines PB - NA CY - NA CP - EDQM. U1 - 1879 U2 - 19-21/03/2011 ER - TY - Generic T1 - Development and validation of a UHPLC-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines Y1 - 2012 A1 - P.Y. Sacré A1 - Eric Deconinck A1 - Chiap,P. A1 - Crommen,J. A1 - Rozet,E. A1 - Patricia Courselle A1 - J.L. de Beer ED - la Caridad KW - detection KW - Development KW - DRUG KW - drugs KW - method KW - Quantification JF - HPLC 2011 CP - Hungarian Society for Separation Sciences U1 - 1872 U2 - 19-23/06/2011 ER - TY - Generic T1 - Development of a fast chromatographic method for screening and quantification of illegal whitening agents Y1 - 2012 A1 - B. De Smet A1 - De Paepe,K. A1 - V Rogiers A1 - J.L. de Beer A1 - Eric Deconinck KW - a KW - Agent KW - Agents KW - detection KW - Development KW - Life KW - Medicine KW - method KW - Quantification KW - Research KW - School KW - SCREENING KW - VALIDATION KW - whitening JF - Research Unlimited, second PhD Day of the Doctoral School of Medicine and Life Sciences-VUB PB - NA CY - NA CP - Vrije Universiteit Brussel U1 - 2045 U2 - 27/05/2012 ER - TY - Generic T1 - Estimation of total exposure to aluminium of the Belgian adult population Y1 - 2012 A1 - V. Fekete A1 - Eric Deconinck A1 - F. Bolle A1 - Joris Van Loco ED - Hajslova,J. ED - Nielsen,M. KW - Adult KW - Adult-population KW - Aluminium KW - analysis KW - Belgian KW - estimation KW - exposure KW - food KW - Food Analysis KW - POPULATION JF - Recent Advances in Food Analysis CP - Hajslova,J., Nielsen,M. U1 - 1912 U2 - 1/11/2011 - 4/11/2011 ER - TY - Generic T1 - Illegal whitening cosmetics: development and validation of a fast chromatographic method for characterisation and risk evaluation of skin penetrating actives Y1 - 2012 A1 - B. De Smet A1 - Eric Deconinck A1 - J.L. de Beer A1 - De Paepe,K. A1 - V Rogiers ED - Université de la Grande Motte KW - Development KW - EVALUATION KW - method KW - risk KW - SKIN KW - VALIDATION JF - Perspectives in percutaneous penetration conference CP - Université de la Grande Motte U1 - 2044 U2 - 10/04/2012-14/10/2012 ER - TY - Generic T1 - Impurity fingerprints for the identification of counterfeit medicines - a feasibility study. Y1 - 2012 A1 - P.Y. Sacré A1 - Eric Deconinck A1 - Dazsykowsky,M A1 - Patricia Courselle A1 - R. Van Cauwenberghe A1 - Chiap,P. A1 - Crommen,J. A1 - J.L. de Beer ED - la Caridad KW - Medicine JF - HPLC 2011 CP - Hungarian Society for Separation Sciences U1 - 1871 U2 - 19-23/06/2011 ER - TY - JOUR T1 - Modelling aluminium leaching into food from different foodware materials with multi-level factorial design of experiments. JF - Food Addit Contam Part A Chem Anal Control Expo Risk Assess Y1 - 2012 A1 - Fekete, Veronika A1 - Eric Deconinck A1 - Bolle, Fabien A1 - Joris Van Loco KW - Aluminum KW - Aluminum Compounds KW - Beverages KW - Ceramics KW - Cooking and Eating Utensils KW - Diffusion KW - Food Contamination KW - Food Packaging KW - Hot Temperature KW - Humans KW - Hydrogen-Ion Concentration KW - Limit of Detection KW - Models, Chemical KW - Osmolar Concentration KW - Reproducibility of Results KW - Sodium Chloride KW - Solubility KW - Spectrophotometry, Atomic KW - Statistics as Topic KW - Time Factors AB -

To estimate the contribution of aluminium (Al) leaching from different materials used for food preparation and serving to the dietary Al intake, Al release from foodware typically used in everyday life was investigated using multilevel factorial design (MFD) of experiments. For Al characterisation, sample preparation and an analytical method using inductively coupled plasma atomic emission spectroscopy was developed and validated. Parameter influence (temperature: x₁, contact time: x₂, pH: x₃, salt concentration: x₄, viscosity: x₅), was evaluated with analysis of variance suggesting that the influence of viscosity is not significant compared to the other four studied parameters. Therefore, predictive, exponential quadratic regression models were established with x₁-x₄. Cross-validation and a set of independent experiments in real food products were used to test the prediction force of the different models. They both suggest that the quality of the models established for Al foil, Al plate and ceramic ware is satisfactory, but less good for glassware and stainless steel. Indeed, in the studied conditions, leaching from these latter food wares was often close to or even below the limit of quantification suggesting that the principal sources of Al intake from food contact materials during food processing are utensils made of Al and ceramic ware.

VL - 29 CP - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22656325?dopt=Abstract M3 - 10.1080/19440049.2012.688068 ER - TY - THES T1 - Ontwikkeling en validatie van een UHPLC-methode voor de routinebepaling van vermageringsmiddelen in illegale farmaceutische preparaten Y1 - 2012 A1 - Verlinde,K. A1 - Eric Deconinck KW - Counterfeit Drugs KW - de KW - Slimming products KW - UPLC PB - Faculteit Geneeskunde en Farmacie, Vrije Universiteit Brussel CY - Brussels, Belgium U1 - 1877 ER - TY - THES T1 - Ontwikkeling en validatie van een UPLC-methode voor de routinebepaling van foliumzuur in voedingssupplementen Y1 - 2012 A1 - Eric Deconinck A1 - J.L. de Beer KW - de KW - Folic Acid KW - UPLC PB - Katholieke Hogeschool Leuven CY - Leuven U1 - 1876 ER - TY - JOUR T1 - Orthogonal chromatographic descriptors for modelling caco-2 drug permeability JF - J.Chromatogr.Sci. Y1 - 2012 A1 - Eric Deconinck A1 - Verstraete,T. A1 - Van Gyseghem,E. A1 - Y. Vander Heyden A1 - Coomans,D. KW - an KW - AS KW - Belgium KW - Brussels KW - chemistry KW - chromatography KW - data KW - DRUG KW - electronic KW - im KW - Institute KW - IS KW - journal KW - Literature KW - MODEL KW - Multiple KW - ON KW - Permeability KW - regression KW - SCREENING KW - System KW - use AB - The use of chromatographic descriptors as alternative for Caco-2 permeability in drug absorption screening was evaluated. Therefore, retentions were measured on 17 Reversed-Phase Liquid Chromatographic systems, considered to be orthogonal or dissimilar, and an Immobilized Artificial Membrane (IAM) system. Retentions on a Micellar Liquid Chromatography system were taken from the literature. From this set of systems, those found dissimilar for the used data set were selected. The retention factors on these systems were then used as descriptors in QSAR modelling. Modelling was performed using Stepwise Multiple Linear Regression. This resulted in a model using only two chromatographic systems with good descriptive and acceptable predictive properties. A high qualitative model was obtained by combining both chromatographic systems selected in the previous model with a lipophilicity parameter (the squared Moriguchi n-octanol/water partition coefficient) and the molecular volume VL - 50 CP - 3 U1 - 1867 M3 - http://dx.doi.org/10.1093/chromsci/bmr044 ER - TY - JOUR T1 - The quality coefficient as performance assessment parameter of straight line calibration curves in relationship with the number of calibration points JF - Accreditation and Quality Assurance Y1 - 2012 A1 - J. De Beer A1 - Naert,C. A1 - Eric Deconinck KW - AS KW - assessment KW - Calibration KW - performance KW - Quality AB - cfr. artikel VL - 17 CP - 3 U1 - 2038 M3 - http://dx-doi.org/10.1007/s00769-011-0871-1 ER - TY - RPRT T1 - Spectroscopic Detection of Counterfeit Cialis Y1 - 2012 A1 - P.Y. Sacré A1 - Eric Deconinck A1 - De Beer,T.R. A1 - Patricia Courselle A1 - R. Van Cauwenberghe A1 - Chiap,P A1 - Crommen,J. A1 - J.L. de Beer KW - Counterfeit Drugs KW - detection PB - WIV-ISP CY - Brussels U1 - 1880 ER - TY - JOUR T1 - A validated GC-MS method for the determination and quantification of residual solvents in counterfeit tablets and capsules. JF - J Pharm Biomed Anal Y1 - 2012 A1 - Eric Deconinck A1 - Michael Canfyn A1 - Sacré, P-Y A1 - S. Baudewyns A1 - Patricia Courselle A1 - De Beer, J O KW - Calibration KW - Capsules KW - Counterfeit Drugs KW - Drug Contamination KW - Fraud KW - Gas Chromatography-Mass Spectrometry KW - Limit of Detection KW - Reference Standards KW - Reproducibility of Results KW - Solvents KW - Tablets KW - Temperature KW - Time Factors AB -

A fast headspace GC-MS method was developed and validated for the detection and quantification of residual solvents of all three ICH-classes in counterfeit tablets and capsules. The method was validated for 10 solvents, selected based on an initial screening of counterfeit medicinal products. The considered solvents were ethanol, 2-propanol, acetone, ethylacetate, chloroform, carbon tetrachloride, benzene, toluene, dichloromethane and ethylbenzene. The proposed method uses a Phenomenex 624 capillary column (60 m × 0.32 mm; 1.8 μm film thickness) (Phenomenex, Torrance, USA) with an oven temperature program from 60 °C (held for 5 min) to 270 °C at 25 °C/min. 270 °C is held for 10 min. The total run time is 23.4 min. The obtained method was fully validated by applying the "total error" profile. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were smaller than 5%, the β-expectation tolerance limits did not exceed the acceptance limits of ±10% and the relative expanded uncertainties were acceptable for all of the considered components. A method was obtained for the screening and quantification of residual solvents in counterfeit tablets and capsules, which will allow a fast screening of these products for the presence of residual solvents.

VL - 70 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22683230?dopt=Abstract M3 - 10.1016/j.jpba.2012.05.022 ER - TY - JOUR T1 - A validated Ultra High Pressure Liquid Chromatographic method for the characterisation of confiscated illegal slimming products containing anorexics. JF - J Pharm Biomed Anal Y1 - 2012 A1 - Eric Deconinck A1 - Verlinde, K A1 - Patricia Courselle A1 - Beer, J O De KW - Appetite Depressants KW - Calibration KW - Chromatography, High Pressure Liquid KW - Dietary Supplements KW - Drug Combinations KW - Drug Contamination KW - Limit of Detection KW - Linear Models KW - Reference Standards KW - Reproducibility of Results AB -

A fully validated UHPLC-DAD method for the identification and quantification of pharmaceutical preparations, containing molecules frequently found in illegal slimming products (sibutramine, modafinil, ephedrine, nor-ephedrine, metformin, theophyllin, caffeine, diethylpropion and orlistat) was developed. The proposed method uses a Vision HT C18-B column (2 mm × 100 mm, 1.5 μm) with a gradient using an ammonium acetate buffer pH 5.0 as aqueous phase and acetonitrile as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile). Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 3.0% and 1.5%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 3% for all of the considered components. A UHPLC-DAD method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations and which can, if necessary, be coupled to a MS-detector for a more thorough characterisation.

VL - 59 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22075376?dopt=Abstract M3 - 10.1016/j.jpba.2011.09.036 ER - TY - Generic T1 - A validated ultra high pressure liquid chromatographic method for qualification and quantification of folic acid in pharmaceutical preparations Y1 - 2012 A1 - Eric Deconinck A1 - S Crevits A1 - P. Baten A1 - Patricia Courselle A1 - J. De Beer ED - Belgian Society of Pharmaceutical Sciences KW - acid KW - ALL KW - an KW - Analyses KW - analysis KW - Area KW - AS KW - at KW - bias KW - Comparison KW - differences KW - DRUG KW - effect KW - Folic Acid KW - function KW - LEVEL KW - levels KW - measurement KW - method KW - ON KW - organic KW - parameters KW - ph KW - Pharmaceutical Preparations KW - Pressure KW - profile KW - Quantification KW - Reproducibility KW - response KW - result KW - results KW - Sample KW - Samples KW - separation KW - Size KW - Statistical KW - Still KW - System KW - Test KW - time KW - tolerance KW - UPLC KW - variation KW - variations KW - WATER KW - waters AB - A fully validated HPLC-method for the identification and quantification of folic acid in pharmaceutical preparations was transferred to UPLC. The starting parameters were calculated using the 'Acquity UPLC JF - Drug Analysis 2010 CP - Belgian Society of Pharmaceutical Sciences U1 - 1869 U2 - 21-24/09/2010 ER - TY - JOUR T1 - Detection of counterfeit Viagra® by Raman microspectroscopy imaging and multivariate analysis. JF - J Pharm Biomed Anal Y1 - 2011 A1 - Sacré, Pierre-Yves A1 - Eric Deconinck A1 - Saerens, Lien A1 - De Beer, Thomas A1 - Patricia Courselle A1 - Vancauwenberghe, Roy A1 - Chiap, Patrice A1 - Crommen, Jacques A1 - De Beer, Jacques O KW - Algorithms KW - Chemistry, Pharmaceutical KW - Counterfeit Drugs KW - Discriminant Analysis KW - Excipients KW - Feasibility Studies KW - Fraud KW - Lactose KW - Microspectrophotometry KW - Multivariate Analysis KW - Phosphodiesterase 5 Inhibitors KW - Piperazines KW - Principal Component Analysis KW - Purines KW - Reference Standards KW - Reproducibility of Results KW - Sildenafil Citrate KW - Spectrum Analysis, Raman KW - Sulfones KW - Tablets KW - Technology, Pharmaceutical AB -

During the past years, pharmaceutical counterfeiting was mainly a problem of developing countries with weak enforcement and inspection programs. However, Europe and North America are more and more confronted with the counterfeiting problem. During this study, 26 counterfeits and imitations of Viagra® tablets and 8 genuine tablets of Viagra® were analysed by Raman microspectroscopy imaging. After unfolding the data, three maps are combined per sample and a first PCA is realised on these data. Then, the first principal components of each sample are assembled. The exploratory and classification analysis are performed on that matrix. PCA was applied as exploratory analysis tool on different spectral ranges to detect counterfeit medicines based on the full spectra (200-1800 cm⁻¹), the presence of lactose (830-880 cm⁻¹) and the spatial distribution of sildenafil (1200-1290 cm⁻¹) inside the tablet. After the exploratory analysis, three different classification algorithms were applied on the full spectra dataset: linear discriminant analysis, k-nearest neighbour and soft independent modelling of class analogy. PCA analysis of the 830-880 cm⁻¹ spectral region discriminated genuine samples while the multivariate analysis of the spectral region between 1200 cm⁻¹ and 1290 cm⁻¹ returns no satisfactory results. A good discrimination of genuine samples was obtained with multivariate analysis of the full spectra region (200-1800 cm⁻¹). Application of the k-NN and SIMCA algorithm returned 100% correct classification during both internal and external validation.

VL - 56 CP - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21715121?dopt=Abstract M3 - 10.1016/j.jpba.2011.05.042 ER - TY - JOUR T1 - Development and validation of a ultra-high-performance liquid chromatography-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines. JF - J Chromatogr A Y1 - 2011 A1 - Sacré, Pierre-Yves A1 - Eric Deconinck A1 - Chiap, Patrice A1 - Crommen, Jacques A1 - Mansion, François A1 - Rozet, Eric A1 - Patricia Courselle A1 - De Beer, Jacques O KW - Acetonitriles KW - Analysis of Variance KW - Chromatography, High Pressure Liquid KW - Counterfeit Drugs KW - Linear Models KW - Phosphodiesterase 5 Inhibitors KW - Piperazines KW - Purines KW - Reproducibility of Results KW - Sildenafil Citrate KW - Spectrophotometry, Ultraviolet KW - Sulfones AB -

Pharmaceutical counterfeiting is a permanently growing problem. Control laboratories are constantly analysing counterfeit medicines. In industrialised countries, one of the main counterfeited class of medicines are erectile dysfunction drugs. This paper describes the development and validation of a fast method to detect and quantify the three authorised phosphodiesterase type 5 inhibitors and five analogues. The method is based on the use of a sub-2 microns polar-embedded column with a gradient using acetonitrile as organic modifier and 10mM ammonium formate buffer (pH 3.5) as aqueous component of the mobile phase. The separation was achieved in less than 4.5 min. The method has also been compared to the registered HPLC method for the assay of Viagra(®) which was considered as the reference method. The method is also compatible with on-line coupling mass spectrometry and will significantly reduce analysis times and solvent consumption.

VL - 1218 CP - 37 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21835410?dopt=Abstract M3 - 10.1016/j.chroma.2011.07.029 ER - TY - JOUR T1 - A fast ultra high pressure liquid chromatographic method for qualification and quantification of pharmaceutical combination preparations containing paracetamol, acetyl salicylic acid and/or antihistaminics. JF - J Pharm Biomed Anal Y1 - 2011 A1 - Eric Deconinck A1 - Sacré, P Y A1 - S. Baudewyns A1 - Patricia Courselle A1 - De Beer, J KW - Acetaminophen KW - Analgesics, Non-Narcotic KW - Anti-Inflammatory Agents, Non-Steroidal KW - Aspirin KW - Buffers KW - Calibration KW - Chemistry, Pharmaceutical KW - Chromatography, High Pressure Liquid KW - Drug Combinations KW - Drug Compounding KW - Guidelines as Topic KW - Histamine Antagonists KW - Hydrogen-Ion Concentration KW - Linear Models KW - Quality Control KW - Reproducibility of Results KW - Solvents KW - Technology, Pharmaceutical KW - Temperature KW - Time Factors AB -

A fully validated UHPLC method for the identification and quantification of pharmaceutical preparations, containing paracetamol and/or acetyl salicylic acid, combined with anti-histaminics (phenylephrine, pheniramine maleate, diphenhydramine, promethazine) and/or other additives as quinine sulphate, caffeine or codeine phosphate, was developed. The proposed method uses a Waters Acquity BEH C18 column (2 mm × 100 mm, 1.7 μm) with a gradient using an ammonium acetate buffer pH 4.0 as aqueous phase and methanol as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 1.5% and 2%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 5% for all of the considered components. A UHPLC method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations.

VL - 56 CP - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21665401?dopt=Abstract M3 - 10.1016/j.jpba.2011.05.013 ER - TY - JOUR T1 - Impurity fingerprints for the identification of counterfeit medicines--a feasibility study. JF - Anal Chim Acta Y1 - 2011 A1 - Sacré, Pierre-Yves A1 - Eric Deconinck A1 - Daszykowski, Michal A1 - Patricia Courselle A1 - Vancauwenberghe, Roy A1 - Chiap, Patrice A1 - Crommen, Jacques A1 - De Beer, Jacques O KW - Algorithms KW - Carbolines KW - Chromatography, High Pressure Liquid KW - Counterfeit Drugs KW - Discriminant Analysis KW - Drug Contamination KW - Feasibility Studies KW - Least-Squares Analysis KW - Piperazines KW - Principal Component Analysis KW - Purines KW - Sildenafil Citrate KW - Spectrophotometry, Ultraviolet KW - Sulfones KW - Tablets KW - Tadalafil AB -

Most of the counterfeit medicines are manufactured in non good manufacturing practices (GMP) conditions by uncontrolled or street laboratories. Their chemical composition and purity of raw materials may, therefore, change in the course of time. The public health problem of counterfeit drugs is mostly due to this qualitative and quantitative variability in their formulation and impurity profiles. In this study, impurity profiles were treated like fingerprints representing the quality of the samples. A total of 73 samples of counterfeit and imitations of Viagra(®) and 44 samples of counterfeit and imitations of Cialis(®) were analysed on a HPLC-UV system. A clear distinction has been obtained between genuine and illegal tablets by the mean of a discriminant partial least squares analysis of the log transformed chromatograms. Following exploratory analysis of the data, two classification algorithms were applied and compared. In our study, the k-nearest neighbour classifier offered the best performance in terms of correct classification rate obtained with cross-validation and during external validation. For Viagra(®), both cross-validation and external validation sets returned a 100% correct classification rate. For Cialis(®) 92.3% and 100% correct classification rates were obtained from cross-validation and external validation, respectively.

VL - 701 CP - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21801892?dopt=Abstract M3 - 10.1016/j.aca.2011.05.041 ER - TY - Generic T1 - Nieuwe stok achter de deur tegen valse Viagra Y1 - 2011 A1 - Eric Deconinck KW - de KW - Viagra PB - Belga Media Support U1 - 2098 ER - TY - Generic T1 - Un nouveau moyen de pression contre la contrefaçon de Viagra Y1 - 2011 A1 - Eric Deconinck KW - de KW - Viagra PB - Belga Media Support U1 - 2099 ER - TY - JOUR T1 - A validated ultra high pressure liquid chromatographic method for qualification and quantification of folic acid in pharmaceutical preparations. JF - J Pharm Biomed Anal Y1 - 2011 A1 - Eric Deconinck A1 - Crevits, S A1 - Baten, P A1 - Patricia Courselle A1 - De Beer, J KW - Analysis of Variance KW - Calibration KW - Chromatography, High Pressure Liquid KW - Folic Acid KW - Limit of Detection KW - Pharmaceutical Preparations KW - Reference Standards KW - Reproducibility of Results KW - Vitamins AB -

A fully validated UHPLC method for the identification and quantification of folic acid in pharmaceutical preparations was developed. The starting conditions for the development were calculated starting from the HPLC conditions of a validated method. These start conditions were tested on four different UHPLC columns: Grace Vision HT™ C18-P, C18, C18-HL and C18-B (2 mm × 100 mm, 1.5 μm). After selection of the stationary phase, the method was further optimised by testing two aqueous and two organic phases and by adapting to a gradient method. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. A UHPLC method was obtained for the identification and quantification of folic acid in pharmaceutical preparations, which will cut analysis times and solvent consumption.

VL - 54 CP - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21168299?dopt=Abstract M3 - 10.1016/j.jpba.2010.11.036 ER - TY - JOUR T1 - Comparison and combination of spectroscopic techniques for the detection of counterfeit medicines. JF - J Pharm Biomed Anal Y1 - 2010 A1 - Sacré, Pierre-Yves A1 - Eric Deconinck A1 - De Beer, Thomas A1 - Patricia Courselle A1 - Vancauwenberghe, Roy A1 - Chiap, Patrice A1 - Crommen, Jacques A1 - De Beer, Jacques O KW - Carbolines KW - Least-Squares Analysis KW - Phosphodiesterase Inhibitors KW - Piperazines KW - Principal Component Analysis KW - Purines KW - Sildenafil Citrate KW - Spectroscopy, Fourier Transform Infrared KW - Spectroscopy, Near-Infrared KW - Spectrum Analysis, Raman KW - Sulfones KW - Tadalafil AB -

During this study, Fourier transform infrared spectroscopy (FT-IR), near infrared spectroscopy (NIR) and Raman spectroscopy were applied to 55 samples of counterfeit and imitations of Viagra and 39 samples of counterfeit and imitations of Cialis. The aim of the study was to investigate which of these techniques and associations of them were the best for discriminating genuine from counterfeit and imitation samples. Only the regions between 1800-400 cm(-1) and 7000-4000 cm(-1) were used for FT-IR and NIR spectroscopy respectively. Partial least square analysis has been used to allow the detection of counterfeit and imitation tablets. It is shown that for the Viagra samples, the best results were provided by a combination of FT-IR and NIR spectroscopy. On the other hand, the best results for the Cialis samples were provided by the combination of NIR and Raman spectroscopy (1400-1190 cm(-1)). These techniques not only permitted a clear discrimination between genuine and counterfeit or imitation samples but also the distinction of clusters among illegal samples. This might be interesting for forensic investigations by authorities.

VL - 53 CP - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20542652?dopt=Abstract M3 - 10.1016/j.jpba.2010.05.012 ER - TY - Generic T1 - Detection of counterfeit medicines with infrared spectroscopy Y1 - 2010 A1 - Eric Deconinck A1 - P.Y. Sacré A1 - J.L. de Beer KW - Counterfeit medicines KW - detection KW - Head KW - Medicine JF - 18 th Heads of Medicines Agencies Working Group of Enforcement Officers (h&v) meeting PB - NA CY - NA CP - FAMHP U1 - 2131 U2 - 18-20/10/2010 ER - TY - Generic T1 - Allergenen in geparfumeerde menstruatieproducten Y1 - 0 A1 - Quinten Marcelis A1 - Eric Deconinck A1 - Vera Rogiers A1 - Tamara Vanhaecke A1 - Bart Desmedt ER - TY - Generic T1 - Are injectable SFFC polypeptide drugs safe? : case report demonstrating the presence of haemolytic Bacillus cereus in two illegal polypeptide drugs Y1 - 0 A1 - Steven Janvier A1 - Elke Wattijn A1 - N Botteldoorn A1 - Bart de Spiegeleer A1 - Eric Deconinck A1 - Celine Vanhee ER - TY - THES T1 - Hazard analysis of falsified peptide medicines Y1 - 0 A1 - Steven Janvier A1 - Bart de Spiegeleer A1 - Eric Deconinck A1 - Celine Vanhee ER - TY - Generic T1 - OMCL testing and the API working group: Part of the solution? Y1 - 0 A1 - Eric Deconinck A1 - Jelena Acevska AB -

Within the OMCL network different initiatives were taken to augment the analysis and market surveillance of APIs used by different manufacturers. Despite the efforts, API testing within the network is limited, compared to the surveillance of finished products. Though it has to be said that the risk for quality deficiencies and falsification of APIs is real and was shown by several crisis. Therefore the API-WG organizes atypical market surveillance studies (MSS), where an MSS (analysis according to the Ph. Eur.) is combined with a fingerprint study (MSSFP). An MSS, according to Ph. Eur. only gives an indication of the quality of the product on some distinct parameters, often chosen based on the manufacturing process. A MSSFP study allows to obtain a global image of the sample, to compare to the batches of the (presumed) manufacturer and/or to the data of fingerpint studies performed in the past in order to detect falsifications.

In the presentation the new concept of the combined CAP/MSS/MSSFP studies is presented as well as a summary of the first MSSFP study of this kind on sildenafil citrate (MSSFP004) and this for both the set-up of the study as the obtained results, the conclusion and the lessons learned.

Further the ongoing MSSFP005 study on tadalafil is introduced and some future perspectives for API-fingerprint studies within the OMCL network are discussed. 

JF - Combating Counterfeit and Other Illegal Medicines: 4th Symposium for OMCLs: New trends, new frontiers PB - EDQM CY - Rome, Italy CP - EDQM ER - TY - JOUR T1 - Structural study of l-ascorbic acid 2-phosphate magnesium, a raw material in cell and tissue therapy JF - Journal of biological Inorganic Chemistry Y1 - 0 A1 - X Xu A1 - M Wozniczka A1 - Van Hecke, K A1 - D Buyst A1 - D Mara A1 - C Vervaet A1 - K Herman A1 - Wynendaele, Evelien A1 - Eric Deconinck A1 - De Spiegeleer, Bart VL - 25 CP - 6 M3 - 10.1007/s00775-020-01801-3 ER -