title: 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 microm internal diameter, 31.2cm 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 beta-cyclodextrin (SCD). The best separation was achieved by using 10mM buffer, pH 2.3, containing 5% (mass/volume (m/v)) SCD. Reversed polarity mode was used with an applied voltage of -12kV and the capillary temperature was maintained at 20 degrees C. The method was validated for quantitative determination of the drug. It offered a limit of detection (LOD) of 0.13 microg/ml, a limit of quantitation (LOQ) of 0.4 microg/ml, and a linearity range of 0.4-300 microg/ml. Commercial bulk samples were analyzed using the developed method.
authors.affiliation: Laboratory of Pharmaceutical Analysis, K.U. Leuven, Herestraat 49, B-3000 Leuven, Belgium. fayedaeg@yahoo.com
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Fayed
authors.forename: Soheir A
authors.initials: SA
authors.lastname: Weshahy
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Shehata
authors.forename: Nagiba Y
authors.initials: NY
authors.lastname: Hassan
authors.forename: Jochen
authors.initials: J
authors.lastname: Pauwels
authors.forename: Jos
authors.initials: J
authors.lastname: Hoogmartens
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
mesh_terms: D002021:Buffers; D000077144:Clopidogrel; D003505:Cyclodextrins / Q000737:chemistry; D004340:Drug Contamination; D004560:Electricity; D019075:Electrophoresis, Capillary / Q000191:economics / Q000379:methods*; D005021:Ethylamines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software; D013237:Stereoisomerism; D013696:Temperature; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D002021:Buffers; D003505:Cyclodextrins; D005021:Ethylamines; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; C016162:triethylamine