Capillary electrophoresis for the assay of fixed-dose combination tablets of artesunate and amodiaquine

N’Cho Christophe Amin,Huguette Fabre,Jérôme Montels,Michèle Aké,Marie-Dominique Blanchin

doi:10.1186/1475-2875-11-149

Abstract

BackgroundQuality control of drugs in formulations is still a major challenge in developing countries. For the quality control of artesunate and amodiaquine tablets in fixed-dose combination, only liquid chromatographic methods have been proposed in the literature. There are no capillary electrophoretic methods reported for the determination of these active substances, although this technique presents several advantages over liquid chromatography (long lifetime, low price of the capillary, low volumes of electrolyte consumption) in addition to simplicity. In this paper, a reliable capillary electrophoresis method has been developed and validated for the quality control of these drugs in commercial fixed-dose combination tablets.MethodsArtesunate and amodiaquine hydrochloride in bilayer tablets were determined by micellar electrokinetic capillary chromatography (MEKC). Analytes were extracted from tablets by sonication with a solvent mixture phosphate buffer pH 7.0-acetonitrile containing benzoic acid as internal standard. Separation was carried out on Beckman capillary electrophoresis system equipped with fused silica capillary, 30 cm long (20 cm to detector) × 50 μm internal diameter, using a 25 mM borate buffer pH 9.2 containing 30 mM sodium dodecyl sulfate as background electrolyte, a 500 V cm−1 electric field and a detection wavelength of 214 nm.ResultsArtesunate, amodiaquine and benzoic acid were separated in 6 min. The method was found to be reliable with respect to specificity,linearity of the calibration line (r2 > 0.995), recovery from synthetic tablets (in the range 98–102%), repeatability (RSD 2–3%, n = 7 analytical procedures). Application to four batches of commercial formulations with different dosages gave content in good agreement with the declared content.ConclusionThe MEKC method proposed is reliable for the determination of artesunate and amodiaquine hydrochloride in fixed-dose combination tablets. The method is well-suited for drug quality control and detection of counterfeit or substandard medicines.

Highlights

Quality control of drugs in formulations is still a major challenge in developing countries
Preliminary studies in capillary zone electrophoresis First of all, the possibility of using capillary zone electrophoresis (CZE) was investigated since the pKa values of AS (pKa 4.3 (−)) and AQ hydrochloride (AQH) (pKas 7.1 (+) and 8.1 (+)) show that they can be separated as anion (AS) and cation (AQ)
micellar electrokinetic capillary chromatography (MEKC) can be used for the determination of AS and AQH in fixed-dose combination tablet formulations

Summary

Introduction

Quality control of drugs in formulations is still a major challenge in developing countries. For the quality control of artesunate and amodiaquine tablets in fixed-dose combination, only liquid chromatographic methods have been proposed in the literature. A reliable capillary electrophoresis method has been developed and validated for the quality control of these drugs in commercial fixed-dose combination tablets. Two high performance liquid chromatographic (HPLC) methods using reverse mode separation have been reported for AS and AQ determination in FDC tablets [3,4]. In the method reported by Phadke et al [3], both compounds are assayed in a single run at two different wavelengths (210 nm for AS, 300 nm for AQ) using a diode array detector. In the paper of Gandhi et al [4], internal standardization with artemether is used to determine the two compounds at a unique wavelength (220 nm) using two test solutions.

Methods

Results

Conclusion