液相色谱-串联质谱法测定人血浆氯吡格雷浓度及其生物等效性评价  

Determination of clopidogrel in human plasma by LC-MS/MS and its application to bioequiavailability

作　　者：陈敏纯[1] 鹿成韬[1] 贾艳艳[1] 宋颖[1] 李雪晴[1] 杨静[1] 丁莉坤[1] 文爱东[1] 

机构地区：[1]第四军医大学西京医院药剂科,陕西西安710032

出　　处：《中国医院药学杂志》2012年第6期421-424,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:建立液相色谱-串联质谱法(LC-MS/MS)测定人血浆中氯吡格雷的浓度,研究2种硫酸氢氯吡格雷片的人体药动学及相对生物利用度。方法:血浆样品中加入内标美利曲辛,经乙腈沉淀蛋白提取,采用液相色谱-串联质谱法。用建立的方法测定20例健康男性受试者单剂量口服硫酸氢氯吡格雷受试制剂或参比制剂后的血药浓度,求得药动学参数,并对2种制剂的生物等效性进行评价。结果:在0.02～20 ng·mL-1内呈良好的线性关系,方法回收率98.4%～103.2%,日内、日间RSD均小于15%。单次口服75 mg硫酸氢氯吡格雷受试制剂或参比制剂后的Cmax分别为(1.9±1.5)ng·mL-1和(1.8±1.1)ng·mL-1;tmax分别为(0.8±0.5)h和(1.0±0.8)h;t1/2分别为(3.4±1.6)h和(3.5±1.5)h;AUC(0-48)分别为(4.4±4.3)h·ng·mL-1和(4.4±4.6)h·ng·mL-1;AUC(0-∞)分别为(4.7±4.4)h·ng·mL-1和(4.7±4.7)h·ng·mL-1。受试制剂对参比制剂的相对生物利用度为(98.2±32.8)%。结论:该方法灵敏,无杂质干扰。测得的受试制剂与参比制剂的主要药动学参数之间无明显差异,表明2种制剂在人体内生物等效。OBJECTIVE To determine clopidogrel in human plasma by LC-MS/MS method, and to investigate its pharmacokinetics and relative bioavailability. METHODS Clopidogrel concentrations in plasma precipitated by methyl cyanides were de terminated by LC-MS/MS. The test and reference formulations were given to 20 healthy male volunteers. Pharmacokinetics and bioequivalence were evaluated. RESULTS The calibration curve was linear within the range of 0. 02 - 20 ng. mL 1. The method recovery was 98.4% - 103.2%. RSDs of intra-day and inter-day were less than 15%. After a single oral dose of 75 mg clopidogrel hydrogen sulphate test or reference tablets, the main pharmacokinetic parameters were as follows： Cmax （1. 9 ± 1. 5） ng. mL-1 and（ 1.8 ± 1.1 ） ng.mL-1 ; t max （0. 8 ± 0.5） h and （1.0 ± 0. 8） h;t1/2 （3.4 ± 1.6） h and（3.5 ± 1.5） h; AUC（0-48 ）（4. 4 ± 4. 3） h.ng.mL -1 and（4. 4 ± 4. 6） h.ng.mL-1 ;AUC（0-∞） （4. 7 ± 4. 4） h.ng.mL-1 and（4. 7 ± 4. 7） h.ng.mL-1 , respectively. Relative bioavailability was（98. 2 ± 32. 8） %. CONCLUSION The method is sensitive with no endogenous interference. No significant difference exists among the main pharmacokinetic parameters for the test and reference tablets. The two formulations are bioequivalence.

关 键 词：硫酸氢氯吡格雷 液相色谱-串联质谱 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]