Fighting Poor Quality Medicines: Development, Transfer and Validation of Generic HPLC Methods for Analyzing Two WHO Recommended Antimalarial Tablets

Jérémie Kindenge Mbinze^1,2, Achille Yemoa^1,3, Pierre Lebrun¹, Pierre-Yves Sacré¹, Védaste Habyalimana^1,4, Nicodème Kalenda^1,2, André Bigot³, Eugène Atindehou⁵, Philippe Hubert¹, Roland Djang’eing’a Marini¹

¹University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, Liège, Belgium.
²Laboratoire d’Analyse des Médicaments, Département de Galénique et d’Analyse des Médicaments, Université de Kinshasa, Kinshasa XI, Democratic Republic of Congo.
³UFR Pharmacie, Faculté des Sciences de Santé, Université d’Abomey Calavi, Cotonou, Bénin.
⁴Rwanda Biomedical Center, Medical Procurement and Production Division, Butare, Rwanda.
⁵Université Félix Houphouet Boigny, Abidjan, Côte d’Ivoire.

DOI: 10.4236/ajac.2015.62012                

Abstract

As serious but neglected public health problems, poor quality medicines, i.e. for antimalarial medicines, urged to be fought. One of the approaches is to consider the analytical chemistry and separative techniques. In this study, a generic liquid chromatographic method was firstly developed for the purpose of screening 8 antimalarial active ingredients, namely amodiaquine (AQ), piperaquine (PPQ), sulfalene (SL), pyrimethamine (PM), lumefantrine (LF), artesunate (AS), artemether (AM) and dihydroartemisinine (DHA) by applying DoE/DS optimization strategy. Since the method was not totally satisfying in terms of peak separation, further experiments were undergone applying the same development strategy while splitting the 8 ingredients into five groups. Excellent prediction was observed prior to correlation between retention times of predicted and observed separation conditions. Then, a successful geometric transfer was realized to reduce the analysis time focusing on the simultaneous quantification of two WHO’s recommended ACTs in anti-malarial fixed-dose combination (AM-LF and AS-AQ) in tablets. The optimal separation was achieved using an isocratic elution of methanol-ammonium formate buffer (pH 2.8; 10 mM) (82.5:17.5, v/v) at 0.6 ml/min through a C18 column (100 mm × 3.5 mm, 3.5 μm) thermostated at 25℃. After a successful validation stage based on the total error approach, the method was applied to determine the content of AM/LF or AS/AQ in seven brands of antimalarial tablets currently marketed in West, Central and East Africa. Satisfying results were obtained compared to the claimed contents.

Keywords

Antimalarial, ACT, Simultaneous Determination, Poor Quality Substances, Design of Experiments, Design Space, Method Transfer, Accuracy Profile

Conflicts of Interest

The authors declare no conflicts of interest.

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