Abstract: OBJECTIVE To develop a UHPLC-MS/MS method for the simultaneous determination of simvastatin and its metabolite simvastatin acid in human plasma. METHODS The sample was extracted with diethylether and then separated on an Agilent ZORBAX SB-C₁₈(100 mm×2.1 mm, 3.5 μm), with acetonitrile and 1 mmol?L^-1 ammonium acetate(pH was adjusted to 4.5 by formic acid) as mobile phase eluted by a gradient program at a flow rate of 0.2 mL?min^-1. Detection was performed with multiple reactions monitoring(MRM) using electrospray ionization(ESI). The positive ion scan mode was used to detect simvastatin and lovastatin(IS) while the negative ion scan mode was used to detect simvastatin acid and lovastatin acid(IS). The MRM transitions of m/z 419.4/199.3 and m/z 405.3/199.3 were used to quantify simvastatin and lovastatin while m/z 435.5/115.2 and m/z 421.4/101.2 were used to quantify simvastatin acid and lovastatin acid. RESULTS The calibration curves were linear over the concentration range of 0.2?50 ng?mL^-1(r>0.99) with the lower limit of quantitation 0.2 ng?mL^-1. Both inter- and intra-day relative standard deviations were ≤11.10%. The extraction recoveries of simvastatin and simvastatin acid were ≥63.71%. CONCLUSION The UHPLC-MS/MS method is selective, sensitive, reliable and suitable for pharmacokinetic study of simvastatin.