高效液相色谱-质谱联用法测定人血浆中氯吡格雷的浓度  

Determination of clopidogrel in human plasma by HPLC-MS/MS

作　　者：樊宏伟[1] 李英斌[2] 张雪萌[3] 朱余兵[1] 肖大伟[1] 

机构地区：[1]南京医科大学附属南京第一医院临床药理科,江苏南京210006 [2]南京医科大学附属南京第一医院神经外科,江苏南京210006 [3]南京医科大学临床药学2003级

出　　处：《中国医院药学杂志》2009年第9期731-732,733,734,共4页Chinese Journal of Hospital Pharmacy

基　　金：江苏省医学科技发展基金临床药学课题(编号:P200511)

摘　　要：目的:建立人血浆中氯吡格雷浓度测定的高效液相色谱-质谱联用(HPLC-MS/MS)法,利于进行新药研究。方法:采用Teknokroma C18色谱柱(100mm×2.1mm,5μm);流动相为甲醇-0.1%甲酸水(80∶20);流速0.2mL·min-1;柱温25℃;选择性离子检测(SRM):氯吡格雷[M+H]+,m/z322.1/212.1;内标:那格列奈[M+H]+,318.3/166.2;有机溶剂乙醚-正己烷(4∶1)液-液提取法进行血浆样品的处理。结果:氯吡格雷和内标那格列萘的保留时间分别在4.4min和3.7min,氯吡格雷的线性范围为5～5000ng·L-1;提取回收率大于75%,方法回收率大于90%,日内、日间RSD小于10%(n=5)。结论:本试验方法适用于氯吡格雷制剂的新药临床研究和血药浓度的常规监测。OBJECTIVE To establish a method to detect the concentration of clopidogrel in human plasma by HPLC-MS/ MS, which will be good for new drugs investigation. METHODS Chromatograph was carried out on a Teknokroma C18 column; The mobile phase was methyl alcohol- 0.1% formic acid （80：20） ; The flow rate was set an 0. 2 mL/min. ;Column temperature was 25 ℃ ;SRM： clopidogrel [M ＋ H]^＋ , m/z 322. 1/212. 1; internal standard nateglinide [M ＋ H]^＋ , 318. 3/166. 2; The samples were extracted from plasma with the organic solvent ether-N-hexane （4：1） by liquid-liquid extraetion. RESULTS The retention time of clopidogrel and internal standard nateglinide were approximately 4. 4 min and 3.7 min, respectively. A good linearity was shown in concentration range 5-5 000 ng L^-1 for clopidogrel; The extraction recovery was more than 75 % and the method recovery was more than 90%; The interday or intraday precision was less than 10% in replicate analysis （n = 5）. CONCLUSION It is suitable for the new drugs clinical investigation of elopidogrel, and the convention monitoring of the drug concentration in the plasma.

关 键 词：氯吡格雷 质谱法 高压液相 血药浓度 

分 类 号：R927.2[医药卫生—药学] R973.2