液相色谱-串联质谱法测定辛伐他汀片的人体药动学和生物等效性

目的:建立人血浆中辛伐他汀浓度的液相色谱-串联质谱(LC-MS／MS)测定法,研究健康受试者单剂量口服辛伐他汀受试或参比制剂后的药动学和生物等效性。方法:20名健康男性受试者进行随机双交叉试验,分别单剂量口服20 mg辛伐他汀受试制剂和参比制剂,采用LC-MS／MS以洛伐他汀为内标正离子选择性反应检测测定辛伐他汀血浆浓度,计算两者的药动学参数及相对生物利用度。结果:受试制剂和参比制剂的血药浓度水平一致,主要药动学参数如下:c_(max)分别为(8．0±s 1．9)和(8．1±1．8)μg·L~(-1);t_(max)分别为(1．9±0．3)和(1．9±0．3)h;t_(1/2)分别为(3．7±1．4)和(4．1±2．2)h;AUC_(0～24)分别为(30±8)和(30±6)μg·h·L~(-1);AUC`(0～∞)分别为(30±8)和(31±7)μg·h·L~(-1)。由2种制剂的AUC_(0～24)计算,受试制剂的相对生物利用度为(101±20)%。结论:建立的LC-MS／MS测定法专属、准确、灵敏度适宜。测得辛伐他汀受试制剂和参比制剂生物等效。

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.