Studies on SF antimicrobials, one of the most frequently used medical products, circulating in Europe or other industrialized regions are very scarce. However, case reports of SF antimicrobials have already demonstrated associated adverse drug effects, prolonged illness, deadly outcomes and microbial resistance. The present study, based on suspected samples seized by the Belgian customs and inspection services, aimed to provide systematic and comprehensive understanding of SF antimicrobials by developing analytical methods for monitoring SF antimicrobials and identifying potential hazards to raise public awareness.
Several quality aspects were evaluated. In a first step samples were screened and the dosage of the identified antibiotics was determined. Results showed that all seized samples contained the API they claimed and that no other antimicrobial drugs could be discovered. Though, half of the samples were underdosed, resulting in a potentially lower efficacy which may aggravate illness of patients and induce bacterial resistance. Further, the collected samples were 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). Moreover, the dissolution profiles of SF antimicrobials were compared to the ones of their genuine counterparts. In general, about 30% of the samples contained higher than permitted amounts of impurities. Concerning the dissolution tests, 58% of samples were not compliant as the amount of drug released is under the limit at the time point described by the USP. In addition to that, low equivalences of dissolution profiles between SF antimicrobials and genuine products were demonstrated based on f1 and f2 statistics. Finally a series of tests of microbiological contamination, residual solvents and heavy metals were carried out. The results showed that 35% of samples did not comply with bio-burden testing, and one out of three injectable samples failed sterility testing with contamination of neurotoxin producing Penicillium crustosum. Moreover, it has been found that four out of 51 SF antimicrobials contained an excessive amount of the class two residual solvent dichloromethane. In the pilot study of heavy metals, one out of 15 tested samples was contaminated with vanadium and lead. These sub-quality issues of SF antimicrobials are possibly attributed to non-standard manufacturing practices, improper storage conditions and/or intentional fraud.
Finally, an approach for on site analysis of suspected antimicrobial drugs was developed, based on spectroscopy and chemometric methods, for identification of the API and dosage compliance.
