液相色谱-串联质谱法测定肾移植患者全血中环孢素A及其2种代谢物浓度  

Determination of cyclosporin A and its two metabolites in whole blood of renal transplant patients by LC-MS/MS

作　　者：周茂金[1] 赵永伟[1] 梅如冰[1] 苏美英[1] 董立[1] 丛绍强[1] 周庆秋[1] 刘昌孝[2] 万仁忠[3] 

机构地区：[1]泰安市中心医院,山东泰安271000 [2]天津药物研究院药效动力学与药代动力学国家重点实验室,天津3000193 [3]山东农业大学动物科学院,山东泰安271000

出　　处：《中国医院药学杂志》2011年第1期16-21,共6页Chinese Journal of Hospital Pharmacy

基　　金：山东省医药卫生科技发展计划(2007HZ011);2009年度山东省药学会临床药学奥赛康中青年科研资助项目

摘　　要：目的：建立液相色谱-串联质谱法（LCMS／MS）测定肾移植患者体内环孢素A及其两个代谢物浓度。方法：全血样品用乙腈沉淀蛋白后直接进样分析，流动相为乙腈-10mmol·L^-1甲酸铵溶液甲酸（85：15：0．5，v／v／v），流速0．5mL·min^-1，采用电喷雾离子化源，检测方式为正离子多离子反应监测（MRM）。血药浓度数据用Topfit2．0软件，按非室模型计算药动学参数。结果：对所建分析方法进行了较全面的验证，考察了环孢素A及其代谢物的药动学特征。环孢素A的主要药动学参数谷浓度C0为（74．0±25．9）μg·L^-1，峰浓度Cmax为（566．2±170．3）μg·L^-1，达峰时间tmax为（1．8±0．4）h，消除半衰期t1/2为（4．6±0．9）h，0-12h药时曲线下面积AUG11-12为（2173．5±580．1）μg·h·L^-1。结论：所建方法灵敏，重现性好，选择性强，样品处理简单，可用于环孢素A及其代谢物浓度的监测和药动学研究。OBJECTIVE To establish a sensitive and specific liquid chromatography tandem mass spectrometry （LC-MS/ MS） method for the determination of cyclosporin A （CsA） and its two metabolites in whole blood of renal transplant patients. METHODS After the whole blood samples were precipitated with acetonitrile, the supernatant was directly injected into the LC-MS/MS system. Mobile phase consisted of acetonitrile 10 mmol· L^-1 ammonium formate-formic acid.（85：15：0. 5,v/v/v） at a flow rate of 0. 5 mL· min ^-1. Mass spectrometric detection was carried out by multiple-reaction monitoring （MRM） in positive mode, and an electrospray ionization source （EIS） was employed as the ionization source. The pharmacokinetic parameters of CsA, and its two metabolites were calculated by non-compartmental analysis using Topfit 2. 0 pharmacokinetic software. RESULTS The method was fully validated, the pharmacokinetic characteristics of CsA and its two metabolites were investigated in renal transplant patients. The main pharmacokinetic parameters of CsA were as follows： C0 （74. 0 ± 25.9 μg· L^-1 , Cmax （566.2±170.3μg· L^-1,tmax（1.8±0. 4）h,t1/2（4.6±0. 9）h,AUC0-12（2 173.5±580.1）μg· L^-1, CONCLUSION This LC- MS/MS method developed and validated was sensitive, selective, simple and reproducible. It could be applied to monitoring and pharmacokinetic study of CsA and its metabolites in solid organ transplant patients.

关 键 词：环孢素A 液相色谱串联质谱法 药动学 

分 类 号：R969[医药卫生—药理学]