Pharmacokinetic and bioequivalence studies of simvastatin tablet in healthy volunteers by LC-MS/MS

AIM: To establish a LC-MS/MS method for determination of simvastatin in human plasma,and investigate the pharmacokinetics and bioequivalence of simvastatin tablet in Chinese healthy volunteers.METHODS: 20 male healthy volunteers were randomized to receive a single crossover oral dose of simvastatin reference tablet or domestic tablet.The concentration of simvastatin in plasma was determined by LC-MS/MS.RESULTS: The main pharmacokinetic parameters of test and reference simvastatin tablets were as following: T_(max):(1.8)±(1.3),(2.10)±(1.00) h,C_(max):(7.12)±(1.61),(7.38)±(1.54)(μg·L~(-1)),AUC_((0-24)):(30.50)±(11.25),(30.17)±(10.21)(μg·h·L~(-1)),t_(1/2):(3.90)±(0.78 ),(3.76)±(0.85) h,respectively.F_((0-24)) was((101.2)±(7.8))%.CONCLUSION: The assay method is shown to be sensitive and accurate giving reliable results.The test tablet was bioequivalent to the reference tablet.