A validated LC method for the determination of clopidogrel in pharmaceutical preparations

A stability indicating, reversed-phase high-performance liquid chromatographic method was developed and validated for the determination of clopidogrel in pharmaceutical dosage forms. The determination was performed on a semi-micro column, BDS C8 (250×2.1 mm i.d., 5 μm particle size); the mobile phase consisted of a mixture of 0.010 M sodium dihydrogen phosphate (pH 3.0) and acetonitrile (35:65, v/v), pumped at a flow rate 0.30 ml min-1. The UV detector was operated at 235 nm. The retention times for clopidogrel and naproxen, which was used as internal standard, were 3.08 and 6.28 min, respectively. Calibration graphs are linear (r better than 0.9991, n=6), in concentration range 1.00-3.00 μg ml-1 for clopidogrel. The intra- and inter-day RSD values were less than 1.96%, while the relative percentage error Er was less than 2.0% (n=5). Detection and quantitation limits were 0.12 and 0.39 μg ml-1, respectively. The method was applied in the quality control of commercial tablets and content uniformity test and proved to be suitable for rapid and reliable quality control. © 2002 Elsevier Science B.V. All rights reserved

Determination of the carboxylic acid metabolite of clopidogrel in human plasma by liquid chromatography-electrospray ionization mass spectrometry

A rapid and specific liquid chromatographic-mass spectrometric method has been developed and validated for the determination of the carboxylic acid metabolite of clopidogrel in human plasma. Sulphafurazole was used as internal standard. The samples were subjected to a solid phase extraction procedure using Hypercarb cartridges. The chromatographic separation was performed on a reversed phase porous graphitized carbon column using a mobile phase consisting of 70% methanol in water containing 0.1% (v/v) trifluoroacetic acid, pumped at a flow rate of 0.25mlmin-1. The analytes were detected after positive electrospray ionization using the selected ion monitoring mode of the species at m/z 308 for the carboxylic acid metabolite of clopidogrel, m/z 322 for clopidogrel and m/z 268 for sulphafurazole. Calibration graphs were linear (r>0.9994, n=6), in the range 100-1000ngml-1 for the carboxylic acid metabolite of clopidogrel. The intra- and inter-day R.S.D. values were <3.1%, while the relative error Er was less than -9.6% (n=6). The limits of detection (3.3σ) and quantitation (10σ) for the carboxylic acid metabolite of clopidogrel were found to be 28 and 93ngml -1, respectively. The efficiency of the solid phase extraction procedure for the carboxylic acid metabolite of clopidogrel averaged 74.6%. © 2003 Elsevier Science B.V. All rights reserved