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 . 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 .
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 . 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 .
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.