LC-MS/MS法同时测定大鼠组织中替格瑞洛及代谢物的质量浓度  

Simultaneous determination of ticagrelor and its metabolite in rat tissues by LC-MS/MS

作　　者：郑国艳[1] 刘茜[1] 聂金凤[1] 赵丛俏 王慧莹 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2018年第2期118-124,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立LC-MS/MS法同时测定大鼠组织中替格瑞洛及其代谢物AR-C124910XX质量浓度的方法,并应用于替格瑞洛及其代谢物组织分布的研究。方法组织样品采用乙醚提取,Agilent XDB-C_(18)柱分离;流动相为甲醇-乙腈-体积分数0.1%甲酸水溶液(体积比50∶20∶30),流速为0.7 m L·min^(-1);质谱采用MRM多反应检测模式,正离子方式检测。结果替格瑞洛在0.1~50μg·g^(-1)内线性关系良好,日间、日内精密度RSD均不大于12.7%;AR-C124910XX在0.05~20μg·g^(-1)内呈良好线性关系,日间、日内精密度RSD均不大于10.7%。结论该法适合于测定大鼠组织中替格瑞洛及其代谢物的质量浓度,并为替格瑞洛的进一步临床研究奠定基础。Objective To develop an LC-MS/MS method for the study of the distribution of ticagrelor and its metabolite AR-C124910XX in rat tissues. Methods The tissues samples were extracted with diethyl ether, and the separation was performed on a reversed-phase Agilent XDB-C18 column. The mobile phase contained methanol acetonitrile and 0. 1% formic acid（ V： V： V -- 50： 20： 30）, The flow rate was 0. 7 mL. min-1. Detection was carried out by multiple reaction monitoring with an API 2000 triple quadrupole mass spectrometer equipped with an electrospray ionization source. Results The linear calibration curve was obtained in the range of 0, 1-50μg·g^-1 for ticagrelor and 0. 05-20μg·g^-1 for AR-C124910XX. For ticagrelor the intra-day and inter-day precision RSD was less than 12. 7% and less than 10. 7% for AR-C124910XX. Conclusions The method is suitable for distribution in rat tissues study of ticagrelor and its metabolite AR-C124910XX has been applied to further clinical study.

关 键 词：替格瑞洛 AR-C124910XX 组织分布 液相色谱-质谱/质谱联用 

分 类 号：R917[医药卫生—药物分析学]