Separation and determination of clopidogrel and its impurities by capillary electrophoresis

Abstract

Clopidogrel bisulphate, an anti-platelet drug, has been separated from its impurities, namely impurity A, B and C by capillary zone electrophoresis (CZE) using uncoated fused-silica capillary (50.0 μm internal diameter, 31.2 cm total length). Four factors affected the separation: buffer concentration, pH of the buffer, concentration of the chiral selector and the applied voltage. Optimization and robustness studies were performed with the aid of reduced central composite experimental design. The buffer used was triethylamine-phosphoric acid and the chosen chiral selector was sulphated β-cyclodextrin (SCD). The best separation was achieved by using 10 mM buffer, pH 2.3, containing 5% (mass/volume (m/v)) SCD. Reversed polarity mode was used with an applied voltage of -12 kV and the capillary temperature was maintained at 20 °C. The method was validated for quantitative determination of the drug. It offered a limit of detection (LOD) of 0.13 μg/ml, a limit of quantitation (LOQ) of 0.4 μg/ml, and a linearity range of 0.4-300 μg/ml. Commercial bulk samples were analyzed using the developed method. © 2008 Elsevier B.V. All rights reserved.