UHPLC-MS/MS法检测大鼠血浆中阿帕替尼血浓度及药代动力学研究  

Determination of apatinib in rat plasma by UHPLC-MS/MS and its pharmacokinetics

作　　者：黄乙明 林奕沨 潘文合 朱光辉 HUANG Yi-ming;LIN Yi-feng;PAN Wen-he;ZHU Guang-hui(Department of Pharmacy,Yuying Children’s Hospital,The Second Affiliated to Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China)

机构地区：[1]温州医科大学附属第二医院、育英儿童医院药学部,浙江温州325000

出　　处：《中国临床药理学杂志》2020年第11期1567-1570,共4页The Chinese Journal of Clinical Pharmacology

基　　金：温州市科技局基金资助项目(Y20180736)。

摘　　要：目的建立大鼠血浆中阿帕替尼超高效液相色谱-串联质谱法测定方法。方法用乙腈沉淀法处理样品。色谱柱:ZORBAX Eclipse Plus C18 column(2.1 mm×50.0 mm,1.8μm),流动相:0.1%甲酸水溶液-乙腈,梯度洗脱,流速:0.4 mL·min^-1,进样体积:2μL。电喷雾离子源,在正离子下多反应模式监测。考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应及稳定性。同时,6只SD大鼠单剂量灌胃盐酸伊马替尼30 mg·kg-1后,用超高效液相串联质谱法检测大鼠血浆中阿帕替尼的浓度,用Drug And Statistics (DAS)3.0软件计算药代动力学参数。结果阿帕替尼在20~6000 ng·mL^-1内,线性关系良好,标准曲线为y=1.23×10^-4x+5.94×10^-2(r=0.992 2);日间、日内精密度均小于15%,回收率大于90%,稳定性较好。阿帕替尼的主要药代动力学参数:Cmax为(62.96±45.37)ng·mL^-1,tmax为(1.83±0.75)h,t1/2为(9.03±7.53)h,AUC0-t为(4521.77±1143.76)ng·mL^-1·h。结论本方法快速、灵敏、重复性好,可用于血浆中阿帕替尼含量测定及药代动力学研究。Objective To establish a UHPLC-MS/MS method for the determination of apatinib in rat plasma.Methods Sample was prepared with acetonitrile precipitation.The analytical column was ZORBAX Eclipse Plus C18 column(2.1 mm×50.0 mm,1.8μm).The mobile phase consisted of water containing 0.1%formic acid and acetonitrile with gradient elution.The flow rate was 0.4 mL·min^-1.The injection volume was 2μL.A tandem mass spectrometer equipped with electrospray ionization source was used as detector with multiple reaction monitoring.The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effects and stability of the method were investigated.And the pharmacokinetic study was performed after single oral administration of 30 mg·kg^-1 apatinib to six rats.The pharmacokinetic parameters were calculated by Drug And Statistics(DAS)3.0 software.Results The calibration curve was linear over 20-6000 ng·mL-1 for apatinib,and the standard curve was y=1.23×10^-4x+5.94×10^-2(r=0.9922).Intra-day and inter-day RSDs were<15%,recovery was>90%,the sample was stable.The main pharmacokinetic parameter:Cmax was(62.96±45.37)ng·mL^-1,tmax was(1.83±0.75)h,t1/2 was(9.03±7.53)h,AUC0-t was(4521.77±1143.76)ng·mL^-1·h.Conclusion The method was proved to be rapid,sensitive,repeatable,suitable for the determination and pharmacokinetic investigation of apatinib.

关 键 词：阿帕替尼 超高效液相色谱-串联质谱法 血药浓度 

分 类 号：R979.1[医药卫生—药品]