摘要
目的改进辛伐他汀血药浓度测定方法,研究辛伐他汀的相对生物利用度。方法20名男性健康受试者随机交叉双周期给药,分别口服单剂量辛伐他汀试验制剂及参比制剂40mg后于不同的时间点采血,200μL血样经1mL乙醚1次萃取后,HPLC—MS/MS检测。DAS2.0软件计算两者的药物动力学参数及相对生物利用度,并评价试验制剂的生物等效性。结果辛伐他汀在0.1-20ng·mL^-1线性好,日内或日间差均〈6%.准确度在101%~109%,稳定性良好,萃取回收率≥82%。受试药与对照药的药动学参数t1/2,tmax,Cmax,AUC0-t,AUC0-∞,分别为:(5.3±5.1)h,(2.2±0.7)h,(4.6±3.0)ng·mL^-1,(24.3±15.7)ng·h·mL^-1,(27.5±21.6)ng·h·mL^-1和(4.5±6.7)h,(1.9±0.7)h,(5.0±3.0)ng·mL^-1,(21.4±13.4)ng·h·mL^-1,(23.9±21.2)ng·h·mL^-1。结果显示:单剂量给药后,辛伐他汀受试制剂的相对生物利用度为(113.1%±17.4%)。结论本方法简单,快速,灵敏,成功应用于辛伐他汀生物等效性研究,辛伐他汀试验制剂相对参比制剂生物等效。
Objective To improve the determination of human plasma simvastatin, study the relative bioavailability of Simvastatin tablets, and evaluate the bioequivalence. Methods A single oral dose of 40 mg test and reference formula tions was given to 20 healthy volunteers in a randomized cross-over study. Sample (0.2 mL) was determined by HPLC-MS/MS after being extracted by 1 mL diethyl ether. DAS 2.0 was used to assess the relative bioavailability and bioequivalence of Simvastatin tablets. Results The linear range of the calibration curves was 0.1-20 ng · mL^-1 for simvastatin with a lower limit of quantitation (0.1 ng · ml^-1 ). Within and between run precision was less than 6%. Accuracy ranged from 101% to 109%. The recovery was more than 82%. The main pharmacokinetic parameters t1/2, tmax,Cmax, AUC0-t and AUC0-∞ of the two formulations were as follows: (5.3±5.1) h, (2.2±0. 7) h, (4.6± 3.0) ng'mI. 1, (24.3±15.7) ng·h · mL^-1, (27.5±21.6) ng·h · mL^-1 and (4.5±6.7) h, (1.9±0.7) h, (5.0±3.0) ng·mL^-1, (21.4±13.4) ng·h · mL^-1, (23.9±21.2) ng·h · mL^-1. Relative bioavailabilityof Simvastatin test reference was 113.1% ± 17.4 %. Conehtsion The present method is sensitive and reliable. The method described herein has been successfully used for the bioequivalence study of simvastatin formulation. The test and reference simvastatin tablets are bioequivalent.
出处
《中南药学》
CAS
2009年第1期13-16,共4页
Central South Pharmacy
关键词
辛伐他汀
生物等效性
高效液相色谱串联质谱法
simvastatin
bioequivalence
high-performance liquid chromatography-tandem mass spectrometry