LC-MS/MS法测定肿瘤患者血浆中阿帕替尼浓度及其临床应用  

Determination of apatinib in tumor patients' plasma by liquid chromatography tandem mass spectrometry and its application

作　　者：李力[1] 李贺[2] 刘杏娥[3] 魏楠[3] LI Li;LI He;LIU Xing＇e;WEI Nan(Institute of Clinical Pharmacy,Zhejiang Hospital;Drug Clinical Trial Institution,Zhejiang Hospital;Oncology Department of Zhejiang Hospital,Hangzhou 310013,Zhejiang,China)

机构地区：[1]浙江医院临床药学室 [2]浙江医院临床试验机构 [3]浙江医院肿瘤内科

出　　处：《中国临床药理学与治疗学》2018年第7期790-795,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家科技重大专项项目-老年病新药临床技术平台(2013ZX09303005);浙江省自然科学基金(LQ15H310003);浙江省老年医学重点实验室开放基金(2014-01)资助项目

摘　　要：目的:建立一种快速、灵敏地测定人血浆中阿帕替尼的LC-MS/MS方法,并应用于肿瘤患者的药物浓度测定。方法:选用索拉菲尼作为内标,血浆样品用乙腈直接沉淀蛋白后,色谱柱采用Eclipse Plus C18(2.1 mm×100 mm,3.5μm),流动相为乙腈-10 mmol/L醋酸铵溶液(均含0.1%甲酸)85∶15(V/V),流速为0.25 m L/min,采用电喷雾离子化源,正离子方式,扫描方式为多反应监测(MRM),用于监测的离子反应分别为m/z 398.1→m/z 212.0(阿帕替尼)和m/z 465.3→m/z270.1(内标索拉菲尼)。方法学验证后用于肿瘤患者的血药浓度检测。结果:血浆中内源性物质对测定无干扰,阿帕替尼2.0~2 000.0μg/L范围内线性关系良好(r=0.996 8);4个不同质控浓度水平(定量下限,低、中、高浓度)的准确度96.1%~105.3%范围内;批内(n=5)和批间(n=3)精密度良好,相对标准误差(RSD)均小于15%;阿帕替尼和内标的提取回收78.0%~87.8%,内标归一化阿帕替尼基质效应因子为92.4%~107.3%。结论:本方法特异性强,灵敏度高,符合临床生物样本分析要求,适用于人血浆中阿帕替尼浓度的测定。AIM：To establish a rapid,accurate liquid chromatography-tandem mass spectrometry（LC-MS/MS） method for the determination of apatinib in tumor patients and apply this method to analyze the clinical samples.METHODS：Sorafenib was employed as the internal standard.The analyte and internal standard were extracted from plasma by protein precipitation with acetonitrile and separated on Eclipse Plus C18 column（2.1 mm × 100 mm,3.5 μm）,mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate（85 ∶ 15,V/V,containing 0.1% formic acid） at the flow rate of 0.25 m L/min.Electrospray ionization（ESI） source was applied and operated in the positive multiple reaction monitoring（MRM） mode.The MS/MS ion transitions monitored were m/z 398.1 → m/z 212.0 and m/z 465.3 → m/z 270.1 for apatinib and internal standard,respectively.After methodology validation,this method was applied for the clinical analysis of apatinib in plasma from tumor patients.RESULTS：Chromatograms showed no endogenous interfering peaks with blank samples.The standard curves were demonstrated to be liner in the range of2.0-2 000 μg/L（r = 0.996 8）.The RSD of interday（n = 5） and intra-day（n = 3） for four different concentration levels were less than 15%,The average recoveries were between 78.0% and 87.8%.The internal standard normalized matrix effect92.4% and 107.3%.CONCLUSION：The method is specific,sensitive and suitable for clinical determination of apatinib in tumor patients plasma efficiently.

关 键 词：阿帕替尼 液质联用法 血药浓度 药物动力学 

分 类 号：R917[医药卫生—药物分析学] R969.1[医药卫生—药学]