A simple, rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry (ms) method was developed and validated for the quantification of metaxalone, a skeletal muscle relaxant,in human plasma using metaxalone –d6 as internal standard (is). following liquid-liquid extraction(lle) , the analytes were separated using an isocratic mobile phase on a reverse phase c18 column (chromatopak peerless basic 50´ 4.6mm´ 3.0μm ) and analyzed by ms in the multiple reaction monitoring mode using the respective [m+h]+ ions, m/z 222.14 / 160.98 for metaxalone and m/z 228.25 /167.02 for the is. the assay exhibited a linear dynamic range of 25.19 -2521.313 ng/ml for metaxalone in human plasma. the goodness of fit was consistently greater than 0.98 during the course of validation. the range of accuracy and precision of the back-calculated concentrations of the standard curve points was from 94.1 % to 104.4 % and 0.3 % to 5.6 % for metaxalone a run time of 2.0 min for each sample and injection volume is 5 μl . the validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability, or bioequivalence studies.