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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 method for the determination of simvastatin in human plasma by high performance liquid chromatography-tandem mass spectrometry and to study the pharmacokinetics of simvastatin tablets. Methods: Lovastatin was used as internal standard. The plasma samples were separated by liquid-liquid extraction and analyzed by HPLC-MS / MS. The DAS2.1 program was used to calculate the pharmacokinetic parameters. Results: The linear range of simvastatin plasma concentration was 0.1016 ~ 20.32ng · ml ~ (-1), r = 0.9981. The lower limit of quantitation was 0.1016ng · ml -1. The relative recovery was 85% -115%. The intra-day and inter-day RSD was <11%. The absolute recovery was> 75%. The main pharmacokinetic parameters of simvastatin tablets were AUC_ (0 ~ 24), C_ (max), t_ (max), t_ (1 / 2z) and CL_ (z / F) were 34.34 ± 19.57 ng · h · ml, 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: The established method for the determination of simvastatin concentration in human plasma is sensitive, accurate and reliable and suitable for simvastatin human pharmacokinetic studies.