用UPLC-MS/MS法测定人血浆中他莫昔芬与活性代谢物吲哚昔芬的浓度及应用  

Determination of tamoxifen and its active metabolite Endoxifen in human plasma by UPLC-MS/MS and its application

作　　者：林晓东 王哲 董瑶瑶 陈瑞杰 朱光辉 LIN Xiao-dong;WANG Zhe;DONG Yao-yao;CHEN Rui-jie;ZHU Guang-hui(Department of Pharmacy,The Second Affiliated Hospital&Yuying Children’s Hospital of 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》2024年第1期112-116,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的建立一种快速、简便的超高效液相色谱-串联质谱联用法(UPLC-MS/MS)检测乳腺癌患者血浆中他莫昔芬及其活性代谢物吲哚昔芬的浓度。方法以乙腈为沉淀剂沉淀蛋白,用色谱柱ZORBAX Eclipse plus C_(18)(18μm,2.1 mm×50 mm)进行分离,以甲醇乙腈为流动相,以地西泮为内标物,采用电喷雾离子源、正离子多反应监测模式,检测离子通道为他莫昔芬m/z 372.0→72.1,吲哚昔芬m/z 374.0→58.2,地西泮m/z 285→192.9。结果他莫昔芬和吲哚昔芬分别在1~500 ng·mL^(-1)(R2=0.9995)、0.5~250 ng·mL^(-1)(R2=0.9999)线性关系良好;他莫昔芬及吲哚昔芬在低、中、高3个质控浓度下的日内、日间精密度均小于10%,并在低温放置及反复冻融的条件下稳定性较好。结论本实验结果表明该法符合生物样本分析要求,样品处理简便、专属性强、能够准确快速地测定人血浆中他莫昔芬和吲哚昔芬的浓度。Objective To establish a rapid and convenient UPLC-MS/MS method for the determination of tamoxifen and its active metabolite endoxifen in plasma of patients with breast cancer.Methods With diazepam as the internal standard,the plasma sample was precipitated with acetonitrile and methanol-acetonitrile was used as mobile phase.The samples were separated by chromatographic column ZORBAX Eclipse plus C_(18)(18μm,2.1 mm×50 mm)and scanned by electrospray ion source and positive ion multiple reaction monitoring mode.The ion channels were detected as tamoxifen m/z 372.0→72.1,endoxifen m/z 374.0→58.2 and diazepam m/z 285→192.9.Results The linearity of tamoxifen and endoxifen were good in the concentration range of 1-500 ng·mL^(-1)(R2=0.9995)and 0.5-250 ng·mL^(-1),respectively(R2=0.9999).The intra-day and inter-day precision of low,medium and high quality control concentrations were all less than 10%.Tamoxifen and endoxifen were stable at low temperature and stable after repeated freeze-thaw.Conclusion The experimental results show that the method meets the requirements of biological sample analysis,and the sample treatment is simple,specific,and can be used for the accurate and rapid determination of tamoxifen and indoloxifen in human plasma.

关 键 词：他莫昔芬 吲哚昔芬 超高效液相色谱-质谱(UPLC-MS/MS)联用法 血药浓度 

分 类 号：R97[医药卫生—药品]