Les risques toxicologiques liés aux médicaments de qualité inférieure

Objective: Poor quality medicines regrouping counterfeit/falsified, sub-standards and degraded are a scourge for developing countries (1). Their public health consequences are often observed for cases of low dosage of active ingredients and sometimes for the absence of these. On the basis of the observed facts as well as suspected reported cases, we were interested in deepening the information through laboratory tests.
Methods: Liquid chromatography (LC), thin layer chromatography (TLC), nuclear magnetic resonance (NMR), mass spectrometry (MS), Raman imagery (Rim) and near infrared spectroscopy (NIR) were used as targeted analytical techniques in this study, associated with the principal component analysis (PCA), while the suspect samples were obtained via the public health authorities of the DR Congo, Benin and Rwanda after their seizure.
Results: The observed cases are presented by therapeutic class, namely:
- analgesics: (1) cases of tablets supposed to contain paracetamol and which have caused abnormal adverse effects in patients who have consumed it, namely sedative effects, polyuria and hypotension. Using LC and complementary surveys by people interview, we were able to demonstrate the presence of a benzodiazepine and at very high doses. (2) Cases of paracetamol syrup whose excipient (glycerol) was substituted by diethylene glycol and which had caused the death of a hundred babies. Using the NIR and the PCA, we were able to elucidate this substitution.
- antimalarials: (case 1) cases of arthemether-lumefantrine tablets which had no therapeutic effect. By means of TLC and LC, the absence of these two active ingredients was clearly demonstrated, but the presence of starch was revealed by Rim. (Case 2) case of quinine tablets that had no expected pharmacological effect. The use of several combined techniques (TLC, LC-MS, NMR and Rim) made it possible to demonstrate the presence of a substance with an imidazole structure (antamoeba).
- antibiotics: (1) amoxicillin powder which after reconstitution in hospital caused poisoning of the babies until death for some. The reconstitution of the suspension had revealed the misuse of hydrogen peroxide instead of distilled water. (2) Finally a large-scale study (80 samples of amoxicillin powder) showed that 8% of the samples were above the claimed dosage.
Conclusion: The cases presented indicate that there are effectively poor quality medicines and that they are responsible of public health problems and in particular of toxicity. Appropriate measures should be taken to protect users.