APPLICATION OF DESIGN SPACE OPTIMIZATION STRATEGY TO THE DEVELOPMENT OF LC METHODS FOR SIMULTANEOUS ANALYSIS OF 18 ANTIRETROVIRAL MEDICINES AND 4 MAJOR EXCIPIENTS USED IN VARIOUS PHARMACEUTICAL FORMULATIONS

peer reviewedtAs one of the world’s most significant public health challenges in low- and middle-income countries,HIV/AIDS deserves to be treated with appropriate medicines, however which are not spared from coun-terfeiting. For that, we developed screening and specific HPLC methods that can analyze 18 antiretroviralmedicines (ARV) and 4 major excipients. Design of experiments and design space methodology wereinitially applied for 15 ARV and the 4 excipients with prediction thanks to Monte Carlo simulations andfocusing on rapidity and affordability thus using short column and low cost organic solvent (methanol)in gradient mode with 10 mM buffer solutions of ammonium hydrogen carbonate. Two other specificmethods dedicated to ARV in liquid and in solid dosage formulations were also predicted and opti-mized. We checked the ability of one method for the analysis of a fixed-dose combination composedby emtricitabine/tenofovir/efavirenz in tablet formulations. Satisfying validation results were obtainedby applying the total error approach taking into account the accuracy profile as decision tool. Then, thevalidated method was applied to test two samples coded A and B, and claimed to contain the tested ARV.Assay results were satisfying only for sample B

Altas capacidades: luces y sombras

Poor-quality medicines are a threat to public health in many low- and middle-income countries, and prospective surveys are needed to inform corrective actions. Therefore, we conducted a cross-sectional survey on a sample of products used for children and available in the private market in Kinshasa, Democratic Republic Congo: amoxicillin (AX) and artemether/lumefantrine (AL), powders for suspension, and paracetamol (PC) tablets 500 mg. Overall, 417 products were covertly purchased from 61 wholesalers. To obtain a representative sample, the products were weighted on their market shares and a subset of 239 samples was randomly extracted to undergo in-depth visual inspection locally, and they were chemically assessed at two accredited laboratories in Belgium. Samples were defined of “poor-quality” if they failed to comply with at least one specification of the International Pharmacopoeia (for AL) or United States Pharmacopoeia 37 (for AX and PC). Results are reported according to the Medicine Quality Assessment Reporting Guideline. The visual inspection detected nonconformities in the aspects of antimalarial powders for suspension, and poor-quality labels across all medicine types. According to chemical analysis, 27.2% samples were of poor quality and 59.5% of AL samples were underdosed in artemether. Poor quality was more frequent for locally manufactured antimalarials (83.3%, P = 0.021; 86.4%, P = 0.022) and PC (4.8%, P = 0.000). The poor quality of the surveyed products may decrease the treatment’s efficacy and favor the development of resistances to antimalarials. It is hoped that these findings may guide the corrective actions of the Democratic Republic of Congo Regulatory Authority, which was the main partner in the research

QUALITY EVALUATION OF AMOXICILLIN AND COMBINATION OF AMOXICILLIN – POTASSIUM CLAVULANATE AS PART OF INVESTIGATION OF THE OFFICIAL AND PERIPHERAL DRUG MARKET IN KINSHASA, LUMBUBASHI AND KOLWEZI - DRC.

DÉVELOPPEMENT, VALIDATION ET TRANSFERT DE MÉTHODES ANALYTIQUES GÉNÉRIQUES POUR LUTTER CONTRE LA FALSIFICATION DES MÉDICAMENTS : APPLICATION EN ZONE PÉRIURBAIN

FALSIFICATION DES MÉDICAMENTS EN MILIEU PÉRIURBAIN : TRISTE RÉALITÉ

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Falsification of drugs in peri-urban areas: a sad reality

peer reviewedFalsifying drugs constitutes a scourge, a danger and a threat to public health. If the situation is already alarming at the global level, what could be expected regarding the peri-urban areas of developing countries? In order to better understand the situation in these areas and to improve the consciousness and involvement of the people living in those areas, a study was carried out to evaluate the current status of the pharmaceutical health situation of some cities in Central East and West Africa. The results illustrate the complexity to set up an adequate pharmaceutical system in these areas that seem to escape to the control of the official health authorities. On the other hand, the analytical results carried out by means of generic analytical methods on antibiotic, antimalarial and non-steroidal anti-inflammatory drugs sampled in the peri-urban areas, are revelatory and confirm the sad reality of false drugs in those areas

Les risques sociétaux liés aux médicaments de qualité inférieure

peer reviewe

Toxicological risks associated with poor quality medicines

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.Lutte contre la falsification des médicament

Investigation of the Quality of Antibiotics-Based Amoxicillin for Monitoring of Some Different Medicine Markets of Democratic Republic of Congo

peer reviewedIn order to combat the counterfeiting of drugs, adapted HPLC analytical USP methods were applied to evaluate the quality of the amoxicillin (with or without potassium clavulanate) powder for suspension sold in some Congolese markets. The adaptation has been done by modifying the column dimensions and adjusting the flow rate. According to the intended deployment of these methods in Demo-cratic Republic of Congo (DRC), 3 factors (analyst, day and equipment) were in-volved in the validation step while applying the classic total error measurement approach with an accuracy profile as decision tool. Since adequate results were obtained in terms of selectivity, precision, trueness and accuracy (tolerance limits of life expectancy: -6.0% and 3.8%) for levels of interest concentration, the methods have been considered for routine use on several samples from different provenances and collected in 4 major DRC cities. Out of 278 samples collected, 200 were eligible for analysis from which 28% were found under standards with several figures: pH failure, out of specification for amoxicillin content, absence of potassium clavulanate, physical modifications of the powders. As evidenced by these findings, medicines of low-quality continue to be a major public health problem requiring appropriate action to effectively address this problem