用LC-MS/MS法测定晚期实体瘤患者血浆中安罗替尼的浓度  

Determination of anlotinib in patient plasma with advanced solid tumours by LC-MS/MS

作　　者：沈琦[1] 刘娟 程敏毓[1] 韩奇[1] 李力[1] SHEN Qi;LIU Juan;CHENG Min-yu;HAN Qi;LI Li(Departmentof Pharmacy,Zhejiang Hospital,Hangzhou 310013,Zhejiang Province,China;Department of Respiratory Medicine,Zhejiang Hospital,Hangzhou 310013,Zhejiang Province,China)

机构地区：[1]浙江医院药剂科,浙江杭州310013 [2]浙江医院呼吸内科,浙江杭州310013

出　　处：《中国临床药理学杂志》2023年第14期2089-2093,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划基金资助项目(2020YFC2009001)。

摘　　要：目的 建立测定人血浆中安罗替尼浓度的高效液相色谱-质谱(LC-MS/MS)方法,并监测肿瘤患者的血药浓度。方法 人血浆样本经蛋白沉淀预处理。色谱柱:Agilent Eclipse XDB-C_(18)(100.0 mm×2.1 mm, 3.5μm),流动相:乙腈-0.1%甲酸水溶液,梯度洗脱,流速:0.2 mL·min^(-1)。三重四极杆质谱电喷雾离子源,多反应监测模式正离子扫描。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、稳定性和基质效应。结果 血浆中安罗替尼质量浓度在1.0~1 000.0 ng·mL^(-1)内线性关系良好,其标准曲线为y=1.78×10^(-2)x+4.68×10^(-3)(r=0.992 7),准确度在97.11%~104.72%,日内、日间精密度RSD均<8%。安罗替尼平均提取回收率为77.71%~83.34%,无明显基质效应。5例肿瘤患者使用日剂量为12或8 mg的安罗替尼进行抗血管生成治疗,谷浓度为56.1~103.9 ng·mL^(-1)。结论 该方法简便、快速、准确,适用于肿瘤患者体内安罗替尼血药浓度的监测。Objective To establish high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for quantifying of anlotinib in human plasma and monitoring its concentration in tumor patients.Methods The plasma samples were pretreated by protein precipitation and separation was achieved on an Agilent Eclipse XDB C_(18)column(100.0 mm×2.1 mm,3.5μm).The mobile phase consisted of acetonitrile-0.1%formic acid solution with a gradient program at a flow rate of 0.2 mL.min^(-1).Detection was performed using an electrospray ionization source operating in positive ion multiple reaction monitoring mode.To validate the method,specificity,linearity and quantification limit,precision and recovery,stability and matrix effect were determined.Results Good linearity was shown over the concentration range of 1.0-1000.0 ng·mL^(-1)for anlotinib,and its the calibration curve was y=1.78×10^(-2)x+4.68×10^(-3)(r=0.9927).The accuracies were between 97.11%-104.72%.The intra-day and inter-day precisions were less than 8%.The average recoveries ranged 77.71%-83.34%.No significant matrix effects were found during the determination.Five tumor patients were administrated 8 mg or 12 mg anlotinib for anti-angiogenic treatment,and the trough concentration range of anlotinib was 56.1-103.9 ng·mL^(-1).Conclusion A simple,rapid and accurate LC-MS/MS method was developed for monitoring the concentration of anlotinib in tumor patients plasma.

关 键 词：安罗替尼 高效液相色谱-质谱联用法 谷浓度 治疗药物监测 

分 类 号：R979.1[医药卫生—药品]