Laboratoire de Chimie Analytique, Contrôle Physico-Chimique des Médicaments, Institut des Biomolécules Max Mousseron, UMR 5247, Faculté de Pharmacie, Montpellier, BP 14491-34093, France.
Malar J. 2012 May 3;11:149. doi: 10.1186/1475-2875-11-149.
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. 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.
Artesunate 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.
Artesunate, 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 (r(2) > 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.
The 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.
在发展中国家，药物制剂的质量控制仍然是一个主要挑战。对于青蒿琥酯和氨酚喹啉固定剂量复方片剂的质量控制，文献中仅提出了液相色谱法。虽然该技术除了简单之外，还具有优于液相色谱法的几个优点（长寿命、毛细管价格低廉、电解质消耗体积小），但尚未报道用于测定这些活性物质的毛细管电泳法。本文开发并验证了一种可靠的毛细管电泳法，用于商业固定剂量复方片剂中这些药物的质量控制。
双层片剂中的青蒿琥酯和盐酸氨酚喹啉采用胶束电动毛细管色谱法（MEKC）测定。通过超声处理用含苯甲酸钠作为内标物的磷酸盐缓冲液 pH 7.0-乙腈溶剂混合物从片剂中提取分析物。在配备熔融石英毛细管、30 cm 长（20 cm 至检测器）×50 μm 内径的贝克曼毛细管电泳系统上进行分离，使用 25 mM 硼酸盐缓冲液 pH 9.2 作为背景电解质，施加 500 V cm(-1) 电场和 214 nm 的检测波长。
青蒿琥酯、氨酚喹啉和苯甲酸在 6 分钟内得到分离。该方法具有良好的专属性、校准曲线的线性（r(2) > 0.995）、从合成片剂中的回收率（在 98-102%范围内）、重复性（RSD 2-3%，n = 7 个分析程序）。应用于四种不同剂量的商业制剂批次，其含量与宣称含量相符。
所提出的 MEKC 方法可用于测定固定剂量复方片剂中的青蒿琥酯和盐酸氨酚喹啉。该方法适用于药物质量控制和检测假冒或劣质药品。
