title: 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.
abstract: As 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 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 10mM 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.
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium; Rwanda Biomedical Center/Medical Procurement and Production Division, P.O. Box 640 Kigali, Rwanda.
authors.forename: Védaste
authors.initials: V
authors.lastname: Habyalimana
authors.affiliation: University of Kinshasa, Faculty of Pharmaceutical Sciences, Laboratory of Drug Analysis, B.P. 212 Kinshasa XI, Democratic Republic of Congo.
authors.forename: Jérémie Kindenge
authors.initials: JK
authors.lastname: Mbinze
authors.affiliation: Ecole de Pharmacie, Faculté des Sciences de la Santé, Laboratoire de Chimie Analytique et Analyse des Médicaments (LCAM), Université d'Abomey Calavi, 01 P.O. Box 526 Cotonou, Benin.
authors.forename: Achille Loconon
authors.initials: AL
authors.lastname: Yemoa
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: Christelle
authors.initials: C
authors.lastname: Waffo
authors.affiliation: Université des Sciences des Techniques et des Technologies de Bamako, Faculté de Pharmacie, Département Science du Médicament, P.O. Box 1746 Bamako, Mali.
authors.forename: Tidiane
authors.initials: T
authors.lastname: Diallo
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: Nicodème Kalenda
authors.initials: NK
authors.lastname: Tshilombo
authors.affiliation: University of Rwanda, School of Medicine and Pharmacy, P.O. Box 3286 Kigali or 30 Butare, Rwanda.
authors.forename: Justin-Léonard Kadima
authors.initials: JK
authors.lastname: Ntokamunda
authors.affiliation: Arlenda s.a., Chaussée verte, 93, B-4470 Saint-Georges-sur-Meuse, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium. Electronic address: rmarini@ulg.ac.be.
authors.forename: Roland Djang'eing'a
authors.initials: RD
authors.lastname: Marini
mesh_terms: D044966:Anti-Retroviral Agents / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D004867:Equipment Design / Q000379:methods; D005079:Excipients / Q000032:analysis* / Q000737:chemistry
chemical_list: D044966:Anti-Retroviral Agents; D005079:Excipients
keywords: Antiretroviral medicines; Application; Design of experiment – design space; Optimization; Validation