A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated for determining rosuvastatin in human pla sma, a new synthetic hydroxyl methyl glutaryl- coenzyme a reductase inhibitor. The analyte and int ernal standard (IS: Fluconazole) were extracted by simple one-step liquid/liquid extraction with Methy l-tert-Butyl Ether. The organic layer was separated and evaporated under a gentle stream of nitrogen at 40± 5°C. The chromatographic separation was performed on an Kromosil, 5μ , 100×4.6mm column with a mobile phase consisting of 5mM Ammonium acetate pH 3.5 : Acetonitrile (10:90v/v) at a flow rate of 0.800ml/min. The retention time of rosuvast atin and internal standard was 1.22 and 1.23 min, respec tively. Triple–quadrupole MS/MS detection was operated in positive mode by multiple reaction moni toring (MRM) using the precursor-to-product combinations of Drug: 482.20/288.20 (m/z) and ISTD: 307.20/220.10 (m/z) the areas of peaks from the analyte and the IS were used for quantification of rosuvastatin. The method was validated according to the FDA guidelines on bioanalytical method validati on. Validation results indicated that the lower lim it of quantification (LLOQ) was 0.1 ng/mL and the assa y exhibited a linear range of 24.979 - 5003.808ng/mL and gave a correlation coefficient (r ) of 0.999 or better. Quality control samples (0.5, 9, 24 and 46 ng/mL) in six replicates from three diffe rent runs of analysis demonstrated an intra-assay precision (RSD) 7.97-15.94%, an inter-assay precisi on 3.19-15.27%, and an overall accuracy (relative error) of < 3.7%. The analyte was stable in human p lasma following three freeze/thaw cycles and for up to 8 weeks following storage at −20 °C. The assay c an be applied to the analysis of rosuvastatin in human plasma samples derived from clinical trials.