Objective To establish a liquid chromatography-tandem mass spectrometric ( LC-MS/MS ) for determination of clopidogrel in human plasma and stability of clopidogrel under different conditions,which was used subsequently to investigate the pharmacokinetics of clopidogrel in healthy Chinese volunteers. Methods Clopidogrel-d4 hydrogen sulfate was used as an internal standard. Separation was achieved on a WATERS Xterra? RP18 column (4.6 mm× 100 mm,3.5μm) with a mobile phase consisting of acetonitrile-0.1% formic acid (66:34) at a flow rate of 1.0 mL.min-1 within 3.2 min. ESI source was applied and operated in positive ion mode and multiple reaction monitoring (MRM). Plasma samples were pretreated by acetonitrile precipitation. Results A good linearity of clopidogrel was obtained in the concentration range of ( 5-5 000 ) ng.L-1. The lower limit of quantification was 5 ng.L-1. The intra-and inter-run precisions at three quality control levels were within 1.3%–9.9%,the relative deviation of the assay was within -6.2%-14.3%. The blood samples were stable when chilled with crushed ice ( 0℃) and cold water ( 4℃) ,as well as kept at room temperature ( 20℃) for 40 min. The plasma QC samples were stable at room temperature ( 20 ℃) for 4 h,at -70℃ for 38 days and during three freeze-thaw cycles. Hemolysis in blood sample drawn didn’ t affect the plasma concentration. The determination and the result of incurred sample reanalysis met the requirements. Conclusion A specific, rapid, sensitive and stable LC-MS/MS method is developed and validated for determination of clopidogrel in human plasma. The method is proven to be suitable for study of the pharmacokinetics of clopidogrel in healthy Chinese volunteers after a single oral dose of 75 mg clopidogrel hydrogen sulphate tablet.