Determination of pharmacokinetics and bioequivalence of simvastatin tablets with LC-MS/MS in Chinese healthy volunteers

AIM:To establish a LC-MS/MS method for the study of the pharmacokinetics and bioequivalence of simvastatin tablets or reference tablets in healthy male Chinese volunteers.METHODS:A single oral dose of 20 mg simvastatin tablets or reference tablets was given to each volunteer according to an open randomized crossover study in 20 healthy males.The concentrations of simvastatin and reference preparations in plasma were determined by LC-MS/MS with positive ion SRM detection using lovastatin as internal standard.The pharmacokinetics and bioavailability were calculated and compared.RESULTS:The main pharmcokinetic parameters after po a single dose of 20 mg simvastatin and reference tablets individually were as follows:C_(max) (8.0±s 1.9)and(8.1±1.8)μg·L~(-1),t_(max),(1.9±0.3)and(1.9±0.3)h,t_(1/2)(3.7±1.4)and(4.1±2.2) h,AUC_(0-24)(30±8)and(30±6)μg·h·L~(-1),AUC_(0-∞)(30±8)and(31±7)μg·h·L~(-1),respectively.The relative bioavailability of the test compared to reference tablets was(101±20)%.CONCLUSION:The LC- MS/MS method is proved to be specific and sensitive.The simvastatin tablets are bioequivalent to the equivalent dose of reference preparation.