Ultra-performance LC MS/MS method for quantification of clopidogrel active metabolite

A sensible ultra-performance LC-MS method was developed and validated for the quantification of clopidogrel active metabolite in human plasma, with clopidogrel D4 as internal standard. Plasma pretreatment involved a one-step protein precipitation with acetonitrile. The separation was performed by reverse-phase chromatography on a C8 column. The method was linear over the concentration range of 1-150 ng/mL. The intra- and inter-day precision values were below 17% and accuracy was from 1.7 to 7.5% at all quality control levels. The lower LOQ was 0.8 ng/mL. Sample analysis time was reduced to 5 min including sample preparation (limited to protein precipitation). The present method was successfully applied to a clopidogrel active metabolite pharmacokinetic study following oral administration to healthy volunteers.