UPLC-MS/MS法同时检测大鼠血浆伊马替尼及其代谢物  

A UPLC-MS/MS method for simultaneous determination of imatinib and its metabolite in rat plasma

作　　者：黄曦[1] 章利亚 郑宇红[1] 肖仲祥 HUANG Xi;ZHANG Li-ya;ZHENG Yu-hong;XIAO Zhong-xiang(Wenzhou Hospital of Traditional Chinese Medicine Pharmacy,Wenzhou 325000,China;Department of Clinical Pharmacy,Yueqing People’s Hospital of Zhejiang Province,Yueqing 325600,China)

机构地区：[1]温州市中医院药剂科,浙江温州325000 [2]乐清市人民医院临床药学室,浙江乐清325600

出　　处：《实用药物与临床》2018年第12期1402-1405,共4页Practical Pharmacy and Clinical Remedies

基　　金：温州市科技计划项目(Y20170693)

摘　　要：目的建立一种同时快速测定大鼠血浆中伊马替尼及其活性代谢产物N-去甲基伊马替尼浓度的超高效液相色谱串联质谱(UPLC-MS/MS)法。方法用乙腈溶剂沉淀血浆蛋白的前处理方法,应用三重四级杆液质联用仪,色谱柱为ACQUITY UPLC BEH C_(18)色谱柱(2. 1 mm×50 mm,1. 7μm);流动相为乙腈-水(含0. 1%甲酸),梯度洗脱,流速为0. 4 ml/min,柱温40℃,以卡马西平为内标;质谱条件:ESI离子源,正离子模式。结果伊马替尼的出峰时间为0. 38 min,线性范围为20～10 000 ng/ml (r^2=0. 999 2),最低定量限为20 ng/ml,回收率为87. 67%～92. 61%,日内、日间精密度RSD均<15%。N-去甲基伊马替尼的出峰时间为0. 36 min,线性范围为1～1 000 ng/ml (r^2=0. 999 5),最低定量限为1 ng/ml,回收率为87. 26%～98. 89%,日内、日间精密度RSD均<15%。结论该法操作简便快速,专属性高,重复性好,灵敏度高,适用于大鼠血浆中伊马替尼及其活性代谢产物N-去甲基伊马替尼的浓度检测。Objective To construct a UPLC-MS/MS method for determining the concentration of imatinib and its active metabolite N-desmethyl imatinib in rat's plasma.Methods The plasma was precipitated by acetonitrile.An ACQUITY UPLC BEH C18(2.1mm×50mm,1.7μm)column was used as the stationary phase on Waters XEVO TQD.The temperature of column was40℃and the mobile phase consisted of acetonitrile and water(containing0.1%formic acid)at gradient elution.The flow rate of the mobile phase was0.4ml/min.The internal standard was carbam-azepine.Results The peak time of imatinib was0.38min.Excellent linear calibration curves of imatinib were ob-tained in the concentration range of20-10000ng/ml(r^2=0.9992).The lower limit of quantification of imatinib was20ng/ml while die average recovery was87.67%-92.61%.The intra-and inter-day RSD both was below15%.The peak time of N-desmethyl imatinib was0.36min.Excellent linear calibration curves of N-desmethyl imatinib were obtained in the concentration range of1-1000ng/ml(r^2=0.9995).The lower limit of quantification of N-desmethyl imatinib was1ng/ml while the average recovery was87.26%-98.89%.The intra-and inter-day RSD both was below15%.Conclusion The UPLC-MS/MS method is simple,quick and accurate with high sensitivity,and it is suitable for the determination of imatinib and its active metabolite N-desmethyl imatinib in rat's plasma.

关 键 词：伊马替尼 N-去甲基伊马替尼 血药浓度 UPLC-MS/MS 

分 类 号：R965[医药卫生—药理学] O657.63[医药卫生—药学]