FORENSIC PHARMACEUTICAL ANALYSIS OF COUNTERFEIT MEDICINES

The World Health Organisation suggests that falsified and substandard medicines (FSMs) constitute approximately 10% of medicines globally with higher figures expected in low and middle income countries (LMICs). To combat the proliferation of FSMs, this study is aimed at developing simple and rapid instrumental methods for the identification and quantification of these medicines. Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy, Raman spectroscopy and two probe Mass Spectrometry (MS) methods were assessed for the rapid screening of tablet dosage forms. These systems were chosen because NO solvent extraction of the sample was required. Comparison with analyses of the tablets by accepted but more time consuming methods (UV-Vis and LC-MS) assessed the quality of the data obtained. Analgesic/antipyretic and antimalarial medicines tablet dosage forms are commonly falsified and for this study tablets were obtained opportunistically from different countries around the world. Reference spectra of appropriate active pharmaceutical ingredients (APIs) and excipients were created, for each method, as part of the identification process. Currently only Raman and ATR-FTIR delivered quantitative results which were based on automated multivariate analysis. For tablets with a single API, Raman and ATR-FTIR provided the simplest route to API confirmation and for tablets with multiple APIs or APIs present at <10%w/w, in the tablet, probe MS methods were superior. Quantitative screening using ATR-FTIR required the samples to be weighed and crushed to produce reproducible data. Comparison of API confirmation tests between trial methods and LC-MS showed complete agreement and the quantitative results were within ±15% of the UV-Vis data. Each of the new tests can be completed in under five minutes and a survey of 69 paracetamol tablets, from around the world, showed that 10% were suspect. Subsequent probe MS showed the presence of a second undeclared API in different samples. More complex tablet formulations, for example the antimalarials were difficult to quantify rapidly. Raman and PCA methods provide a rapid approach to tablet identification within a limited range of possibilities. Factors that may affect Raman spectra of tablets include the expected API, the API levels, different excipients, colours or surface coatings for the tablets. The simplicity, speed and cost effectiveness of the proposed analytical methods make them suitable for use in LMICs. The potential use of these simple analytical methods in addition to already established pharmacopoeia approved (solvent extraction) techniques could help provide more comprehensive data about FSMs globally.