A rapid and accurate reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of oxiracetam in human plasma. Oxiracetam, a highly polar compound, was successfully retained by Atlantis dC18 reversed-phase column and detected with triple-quadrupole tandem mass spectrometry. After addition of internal standard (piracetam) to human plasma, plasma was simply precipitated with two volume of acetonitrile, evaporated and dissolved in 0.1% acetic acid. This method for the determination of oxiracetam was accurate and reproducible, with a limit of quantitation of 0.2microg/ml in human plasma. The standard calibration curve for oxiracetam was linear (r(2) = 0.999) over the concentration range 0.2-40.0microg/ml in human plasma. The intra- and inter-day precision over the concentration range of oxiracetam was lower than 8.3% (relative standard deviation, %R.S.D.), and accuracy was between 92.5 and 106.4%.