HPLC-MS法测定氯吡格雷酸人体尿药浓度及氯吡格雷酸经尿排泄研究  

Determination of Clopidogrel Carboxylic Acid in Human Urine by HPLC-MS and Evaluation of Urinary Clopidogrel Carboxylic Acid Excretion

作　　者：刘园园[1] 唐立超[1] 沙克亚[1] 丁黎[1] 文爱东[2] 杨林[2] 

机构地区：[1]中国药科大学药物分析教研室,江苏南京210009 [2]第四军医大学西京医院国家药品临床研究机构Ⅰ期临床试验研究室,陕西西安710032

出　　处：《药学进展》2010年第10期463-467,共5页Progress in Pharmaceutical Sciences

摘　　要：目的:建立测定氯吡格雷酸人体尿药浓度的高效液相色谱-质谱联用方法,并通过监测硫酸氢氯吡格雷片经健康受试者口服后其主要Ⅰ相代谢物氯吡格雷酸尿药浓度的经时变化过程,考察氯吡格雷酸经尿排泄特征。方法:色谱采用Lichrospher C18柱(150 mm×2.1 mm,5μm),以甲醇-10 mmol.L-1醋酸铵水溶液(含0.1%甲酸)(42∶58)为流动相。质谱采用电喷雾离子源四级杆质谱,以选择性离子监测方式进行正离子检测。6名健康受试者单次口服硫酸氢氯吡格雷片75 mg后,定时收集尿样。采用甲醇直接稀释法处理尿样后,评价氯吡格雷酸经尿排泄特征。结果:氯吡格雷酸在4.780～9 559μg.L-1质量浓度范围内线性关系良好,平均回收率大于93.4%。受试者服药后0～2小时间,氯吡格雷酸经尿排泄速率最大;36小时内有(1.1±0.5)%的氯吡格雷以氯吡格雷酸形式从尿中排出。结论:该测定方法符合生物样品分析要求;氯吡格雷在体内以氯吡格雷酸形式经尿排泄迅速,24小时内基本排泄完全。Objective：To establish a HPLC-MS method for the determination of clopidogrel carboxylic acid,a major phase Ⅰ carboxylic acid metabolite of clopidogrel,in human urine and to investigate its urinary excretion profile after oral administration of cloprdogrel tablets in healthy volunteers.Methods：A lichrospher C18column （150 mm×2.1 mm,5μm） and methanol-10 mmol·L^-1 ammonium containing 0.1 % formic acid （42∶58） as a mobile phase for LC and electrospray ionization source and positive ion mode for MS were used.6 healthy volunteers were orally administered with clopidogrel bisulfate tablets in single dose of 75 mg.Afterwards the urine samples fromthe subjects were collected at different time point sand diluted directly with methandol to evaluate the urinary excretion profile of clopidogrel carboxylic acid.Results：The calibration curve was linear in the range of 4.780 -9 559μg·L-1 for clopidogrel carboxylic acid in urine and the average recovery was more than 93.4 %.After the volunteers took the tablets,the average urinary excretion rate of clopidogrel carboxylic acid was the highestat 0-2 h and （1.1±0.5） % of the oral dose of clopidogrel was excreted in the fromof clopidogrel carboxylic acid in urine within 36 h.Conclusion：The HPLC-MS method meets the requirement of biological sample analysis.After taking,clopidogrel is rapidly excreted and almostcompletely excreted in the form of clopidogrel carboxylic acid in urine within 24 h.

关 键 词：氯吡格雷 氯吡格雷酸 尿药浓度 高效液相色谱-质谱联用 经尿排泄特征 

分 类 号：R969.1[医药卫生—药理学]