A sensitive and reliable liquid chromatography-tandem mass/mass spectrometry (LC-MS/MS) was developed and validated for the determination of an antiepileptic drug, lacosamide, in human plasma.The method involved the addition of 10μL internal standard solution to 0.1ml of plasma samples, followed by liquid-liquid extraction with 0.5 ml of ethyl acetate.After vortexing and centrifugation, 450 μl of supernatant was transferred and evaporated to dryness in a slight stream of nitrogen.The residue was dissolved in 100μl of mobile phase, and 20μl of it was used for LC-MS/MS analysis.The separations were performed on a Diamonsil C8(2) column (100 mm × 2.1 mm i.d.,5μm, Dikma Technologies Inc.USA), with 0.1% formic acid and acetonitrile as mobile phase, and the detection was performed on tandem mass/mass spectrometry by the multiple-reaction monitoring via an electrospray ionization source.The standard curve was linear over the concentration range from 0.2 to 5000ng/ mL.The lower limit of quantification was 0.2 ng/mL using 100μL of human plasma sample.The intra-and inter assay precision and accuracy were found to be less than 13.64 and 10.41%, respectively.This developed analytical method was successfully applied to the pharmacokinetic study of lacosamide in healthy Chinese volunteers.