LC-MS/MS法同时测定血浆中氟马替尼及其代谢产物浓度  

Determination of Flumatinib and Its Two Major Metabolites in Plasma by LC-MS/MS

作　　者：徐月华 钱洲逸 赵杨 黄琼叶 孙鲁宁 王永庆 孙志明 唐雯雯 XU Yuehua;QIAN Zhouyi;ZHAO Yang;HUANG Qiongye;SUN Luning;WANG Yongqing;SUN Zhiming;TANG Wenwen(Department of Pharmacy,People's Hospital of Haian City,Haian 226600,China;Department of Pharmacy,the First Affiliated Hospital,Nanjing Medical University,Nanjing 210029,China;National Center for Monitoring Adverse Drug Reactions in Family Planning,National Health Commission/Jiangsu Health Development Research Centre,Nanjing 210029,China)

机构地区：[1]海安市人民医院药剂科,海安226600 [2]南京医科大学第一附属医院药学部,南京210029 [3]国家卫生健康委计划生育药品不良反应监测中心/江苏省卫生健康发展研究中心,南京210029

出　　处：《医药导报》2023年第12期1779-1784,共6页Herald of Medicine

摘　　要：目的建立一种简便、特异、快速的液相色谱-串联质谱(LC-MS/MS)法同时测定血浆中的氟马替尼及其两种主要代谢物,用于临床治疗药物监测。方法采用LC-MS/MS法,色谱柱选用ACQUITY UPLC HSS T3色谱柱(2.1 mm×50 mm,1.8μm),流动相为乙腈和10 mmol·L^(-1)甲酸铵(含0.1%甲酸)溶液,梯度洗脱,流速为0.5 mL·min^(-1),洗脱时间为6 min,柱温为38℃,在电喷雾离子源正离子模式下采用多反应监测扫描。结果氟马替尼及其代谢产物N-去甲基氟马替尼(M1)和氟马替尼酰胺水解产物(M3)的质量浓度在考察的浓度范围内线性关系良好,方法的精密度、稳定性良好,精密度均小于15%,相对偏差均在±15%范围内,氟马替尼及其代谢物回收率接近100%。结论该方法操作简单,灵敏度高,能够准确测定出氟马替尼及其两种主要代谢产物的血药浓度,为氟马替尼及其代谢物的药动学研究提供依据。Objective A simple,specific and rapid LC-MS/MS method was established to determine flumatinib and its two major metabolites in human plasma for clinical therapeutic drug monitoring.Methods The determination was performed on an ACQUITY UPLC HSS T3 column(2.1 mm×50 mm,1.8μm)with mobile phases consisting of acetonitrile and 10 mmol·L^(-1) ammonium formate(containing 0.1%formic acid)with gradient elution at the flow rate of 0.5 mL·min^(-1).The elution time was 6 min.The temperature of the column was 38℃.The ion source was electrospray ion source and the scanning mode was multiple reaction monitoring scanning in positive ion mode.Results The mass concentrations of flumatinib and its metabolites(flumatinib M1 and flumatinib M3)have a good linear relationship within the concentration range investigated.The precision and stability of the method are good.The precision is less than 15%,and the relative deviation is within±15%.The extraction recoveries of flumatinib and its metabolites approach nearly 100%.Conclusion The method is simple and sensitive,and can accurately determine the plasma concentration of flumatinib and its metabolites,providing a basis for clinical rational drug use.

关 键 词：氟马替尼 液相色谱串联质谱 血药浓度 

分 类 号：R979.1[医药卫生—药品]