高效液相色谱串联质谱法测定人血浆中辛伐他汀浓度及药动学研究

Determination of Simvastin in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry and Pharmacokinetics of Simvastin Tablets

目的:建立高效液相色谱串联质谱法测定人血浆中辛伐他汀浓度,并进行辛伐他汀片的药动学研究。方法:以洛伐他汀为内标,血浆样品经液-液萃取后,经HPLC-MS/MS分离-分析。采用DAS2.1程序计算有关药动学参数。结果:辛伐他汀血浆浓度测定方法线性范围为0.1016～20.32ng·ml^(-1),r=0.9981。定量下限为0.1016ng·ml^(-1),方法相对回收率85%～115%,日内和日间RSD<11%;绝对回收率>75%。辛伐他汀片主要药动学参数AUC_(0～24)、C_(max)、t_(max)、t_(1/2z)、CL_(z/F)分别为(34.34±19.57)ng·h·ml^(-1)、(11.15±11.58)ng·ml^(-1)、(1.89±1.52)h、(5.99±4.93)h、(703.71±428.48)L·h^(-1)。结论:本试验所建立起来的人血浆中辛伐他汀浓度测定法灵敏、准确、可靠,适用于辛伐他汀的人体内药动学研究。

Objective：To establish a high performance liquid chromatography tandem mass spectrometry（HPLC-MS/MS）method for the determination of simvastin in human plasma,and study the pharmacokinetics of simvastin tablets.Method：Plasma samples were extracted with diethyl ether and determined by HPLC-MS/MS using lovastatin as the internal standard.The pharmacokinetic parameters were calculated with DAS 2.1 practical pharmacokinetics program.Result：The calibration curve of simvastin was obtained within the range of 0.1016-20.32 ng·ml^-1with good linearity（r=0.998 3）.The LOQ of simvastin in plasma was 0.1016ng·ml^-1.The relative recovery was 85%-115%,the intra-and inter-day RSDs were both less than 11%,and the absolute recovery was more than 75%.The parameters of AUC0-24,Cmax,tmax,t1/2zand CL2/Ffor simvastin were（34.34±19.57）ng·h·ml^-1,（11.15±11.58）ng·ml^-1,（1.89±1.52）h,（5.99±4.93）h and（703.71±428.48）L·h^-1,respectively.Conclusion：This method has good sensitivity and precision and is suitable for the pharmacokinetic studies of simvastin in Chinese healthy volunteers.