LC-MS/MS法测定人血浆氯吡格雷酸浓度及其生物等效性评价  

LC-MS/MS determination of clopidogrel acid in human plasma and its application in evaluating bioequiavailability

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

机构地区：[1]第四军医大学西京医院药剂科,西安710032

出　　处：《中国新药杂志》2012年第24期2924-2927,2935,共5页Chinese Journal of New Drugs

摘　　要：目的:建立液相色谱-串联质谱法测定人血浆中氯吡格雷酸的浓度,研究2种硫酸氢氯吡格雷片的人体药代动力学及相对生物利用度。方法:血浆样品中加入内标吡格列酮,经甲醇沉淀蛋白提取,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,求得药代动力学参数,并对2种制剂的生物等效性进行评价。结果:在0.01～10mg.mL-1内呈良好的线性关系,方法回收率93.5%～101.4%,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(3.79±1.9)和(3.42±2.0)mg.mL-1;Tmax分别为(0.80±0.4)和(0.90±0.6)h;t1/2分别为(5.06±0.9)和(5.63±0.9)h;AUC0～48分别为(7.96±3.1)和(8.55±3.7)h.mg.mL-1;AUC0～∞分别为(8.28±3.2)和(9.06±3.9)h.mg.mL-1。受试制剂对参比制剂的相对生物利用度为(96.8±20.9)%。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代动力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 acid in human plasma by LC-MS/MS method,and to investigate its pharmacokinetics and relative bioavailability.Methods： Clopidogrel acid concentrations in plasma precipitated by methanol were determined by LC-MS/MS.The test and reference formulations were administered to 20 healthy male volunteers,and the pharmacokinetics and bioequivalence were evaluated.Results： The calibration curve was linear in the range of 0.01-10 mg·mL^-1.The method recovery was 93.5%-101.4%.The intra-day and inter-day RSDs were less than 15%.After orally taking a single dose of test or reference tablets of 75 mg clopidogrel hydrogen sulphate,the main pharmacokinetic parameters were as follows： Cmax,（3.79±1.9） and（3.42±2.0） mg·mL^-1;Tmax,（0.80±0.4） and（0.90±0.6） h;t1/2,（5.06±0.9） and（5.63±0.9） h;AUC0~48,（7.96±3.1） and（8.55±3.7） h·mg·mL^-1;AUC0~∞,（8.28±3.2） and（9.06±3.9） h·mg·mL^-1,respectively.Relative bioavailability was（96.8±20.9）%.Conclusion： The method is sensitive with no endogenous interference.No significant difference exists among the main pharmacokinetic parameters of the test and reference tablets.The two formulations are bioequivalent.

关 键 词：硫酸氢氯吡格雷 液相色谱-串联质谱 药代动力学 生物等效性 

分 类 号：R912[医药卫生—药学]