Védaste Habyalimana

Application of an innovative design space optimization strategy to the development of LC methods for the simultaneous screening of antibiotics to combat poor quality medicines

The poor quality of medicines is a crucial problem of public health. Therefore, it is important to have analytical tools to attend decisions of the legal authorities while combating this offense. In this context, the main objective of this study was to develop generic methods able to trace, screen and determine several antibiotics and common associated molecules by mean of liquid chromatographic techniques. For that purpose, an innovative Design Space optimization strategy was applied, targeting 16 antibiotics and 3 beta-lactamase inhibitors. The robustness of the developed method allowed using its use in an environment where operational factors such as temperature are not easy to control and eased its transfer to Ultra High Performance Liquid Chromatography. To demonstrate its ability to quantify the targeted molecules, the developed and transferred method was fully validated for two active ingredients commonly used in association, sulbactam and ceftriaxone, using the accuracy profile as decision tool. Based on this successful step, the method was then used for the quantitative determination of these two active ingredients in three pharmaceutical brands marketed in the Democratic Republic of Congo. Two out of the three pharmaceutical products did not comply with the specifications.

Development, validation and comparison of NIR and Raman methods for the identification and assay of poor-quality oral quinine drops

Poor quality antimalarial drugs are one of the publics major health problems in Africa. The depth of this problem may be explained in part by the lack of effective enforcement and the lack of efficient local drug analysis laboratories. To tackle part of this issue, two spectroscopic methods with the ability to detect and to quantify quinine dihydrochloride in childrens oral drops formulations were developed and validated. Raman and near infrared (NIR) spectroscopy were selected for the drug analysis due to their low cost, non-destructive and rapid characteristics. Both of the methods developed were successfully validated using the total error approach in the range of 50-150% of the target concentration (20%W/V) within the 10% acceptance limits. Samples collected on the Congolese pharmaceutical market were analyzed by both techniques to detect potentially substandard drugs. After a comparison of the analytical performance of both methods, it has been decided to implement the method based on NIR spectroscopy to perform the routine analysis of quinine oral drop samples in the Quality Control Laboratory of Drugs at the University of Kinshasa (DRC).

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

HIGHLIGHTSSelection of antiretroviral medicines currently used in Rwanda.Application of design of optimization and design space.Optimization of three methods, generic and dedicated.Application of the developed analytical method. ABSTRACT As one of the worlds 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 counterfeiting. For that, we developed screening and specific HPLC methods that can analyze 18 antiretroviral medicines (ARV) and 4 major excipients. Design of experiments and design space methodology were initially applied for 15 ARV and the 4 excipients with prediction thanks to Monte Carlo simulations and focusing 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 specific methods dedicated to ARV in liquid and in solid dosage formulations were also predicted and optimized. We checked the ability of one method for the analysis of a fixed‐dose combination composed by emtricitabine/tenofovir/efavirenz in tablet formulations. Satisfying validation results were obtained by applying the total error approach taking into account the accuracy profile as decision tool. Then, the validated 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.

Detection of Poor Quality Artemisinin-based Combination Therapy (ACT) Medicines Marketed in Benin Using Simple and Advanced Analytical Techniques

BACKGROUND Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa which bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality controls. METHODS 12 samples of artemether/lumefantrine were collected from formal and informal drug sellers in Cotonou (Benin) as well as additional other similar samples from Rwanda (13 samples) and from D.R. Congo (9 samples). Thin Layer Chromatography (TLC) as classical and simple identification test was applied in Benin while an analytical chemistry laboratory in Belgium (ULg, Pharmacy Department) was asked for further analyses with HPLC and Raman spectroscopy using a developed and validated HPLC method for rapid analysis of artemether/lumefantrine. RESULTS The results obtained in Belgium confirmed the lack of the two active ingredients in the suspected sample of ACT medicine from Benin whereas some samples from Rwanda and D.R. Congo were found to present risk of substandard drugs either for under-dosing or over-dosing. CONCLUSIONS Counterfeit/falsified of artemisinin-based combination therapy (ACT) medicines are really scourge that needs to be fought through strong collaboration between public health authorities and appropriate quality control laboratories.