Stratégies analytiques pour la détection de contrefaçons de médicaments de la dysfonction érectile

Abstract

Since the late eighties, when it was first mentioned, the worldwide phenomenon of pharmaceutical counterfeiting is growing. Belgian customs often encounter presumed counterfeited medical products in Belgian airports and ports because of their central position in Europe and their importance in the transit of goods. Further and deeper analyses are required to assess the counterfeit character of these goods and to provide a scientific basis for the eventual legal procedure. As reference laboratory for the federal agency for medicines and health products (FAMHP), the Scientific Institute of Public Health (IPH) frequently analyses illegal and counterfeit pharmaceutical preparations. The present research project was started with the objective of evaluating several existing methods and developing new analytical methods to detect counterfeit erectile dysfunction drugs. This thesis is focused on the analysis of illegal samples of phosphodiesterase type 5 inhibitors (PDE5-i) containing drugs because these are the most counterfeited pharmaceutical specialities in Belgium. The research was divided into a spectroscopic and a chromatographic part: Infrared based spectroscopies have already demonstrated their ability to detect counterfeit drugs. The first part of the study evaluates the capacity of each technique (mid-infrared (mid-IR), near-infrared (NIR) and Raman spectroscopy) separately and their combinations to discriminate genuine from illegal tablets. Then, the Classification And Regression Trees (CART) algorithm has been used to classify the different samples following the classification system of the Dutch National Institute for Public Health and the Environment (RIVM). The second spectroscopic approach used Raman microspectroscopy mapping to detect counterfeited Viagra®. This technique allows the detection of different compounds according to their Raman spectrum but also the study of the distribution of a selected ingredient among the core of a tablet. The chromatographic part consists of the development and validation of a new Ultra High Pressure Liquid Chromatography method coupled with a UV diode array detector (UHPLC-DAD) and compatible with mass spectrometry (MS) to detect and quantify the three authorised phosphodiesterase type 5 inhibitors (sildenafil, tadalafil and vardenafil) and five of their analogues in illegal pharmaceutical preparations. This method has been validated between +/- 5% acceptance limits using the total error approach and has been compared to the official Viagra® assay method. The ability of HPLC-UV impurity fingerprints to detect illegal samples and to predict whether a new unknown sample is genuine has also been evaluated. The developed analytical methods may be included in a general approach to detect counterfeit drugs containing PDE5-i. This generic approach may also be used to detect other types of counterfeited drugs but should therefore be adapted for each type of medicine