LC-MS/MS法测定人血浆中吡咯替尼的浓度及其临床应用  

Determination of Pyrrotinib Concentration in Human Plasma by LC-MS/MS and Its Clinical Application

作　　者：赵振寰[1] 荆伟丽[1] 刘涛[1] 吕志强[1] 曹志红[1] 徐文[1] ZHAO Zhenhuan;JING Weili;LIU Tao;LYU Zhiqiang;CAO Zhihong;XU Wen(Dept.of Pharmacy,the Affiliated Hospital of Qingdao University,Shandong Qingdao 266003,China)

机构地区：[1]青岛大学附属医院药学部,山东青岛266003

出　　处：《中国药房》2021年第22期2767-2771,共5页China Pharmacy

基　　金：山东省自然科学基金资助项目(No.ZR2017MH045);山东省中医药科技发展计划项目(No.2019-0394);山东省医学会治疗药物监测科研基金项目(No.YXH2020ZX042)。

摘　　要：目的:建立测定吡咯替尼血药浓度的方法,并应用于临床。方法:血浆样本经甲醇沉淀蛋白后,以伊马替尼为内标,采用液相色谱-串联质谱(LC-MS/MS)法测定。以Ultimate AQ-C_(18)为色谱柱,以甲醇(含0.1%甲酸)-水(0.1%甲酸)为流动相进行梯度洗脱,流速为0.4 mL/min,柱温为40℃,进样量为5μL。离子源为电喷雾离子源,以多反应监测模式进行正离子扫描,用于定量分析的离子对分别为m/z 583.4→138.3(吡咯替尼)、494.5→393.4(内标)。选择2020年6-11月于青岛大学附属医院接受吡咯替尼治疗的乳腺癌患者30例,测定其用药1周后的吡咯替尼稳态谷浓度。结果:吡咯替尼检测质量浓度的线性范围为5~300 ng/mL(r=0.9993),定量下限为5 ng/mL;日内、日间RSD均不高于9.30%,相对误差为-6.70%~5.04%;稳定性试验的相对误差为-1.92%~5.42%;提取方法、基质效应、残留效应均不影响待测物的定量分析。30例乳腺癌患者体内吡咯替尼的稳态谷浓度为32.6~82.8 ng/mL,平均血药浓度为53.8 ng/mL,存在2.54倍的个体差异。结论:所建LC-MS/MS法操作简便、灵敏度和准确度较高,可用于乳腺癌患者体内吡咯替尼的血药浓度监测。OBJECTIVE:To establish a method for the determination of pyrrotinib concentration in plasma,and apply it in clinic.METHODS:After precipitated with methanol,the plasma sample was determined by LC-MS/MS using imatinib as internal standard.The determination was performed on Ultimate AQ-C_(18) column with mobile phase consisted of methanol(containing 0.1%formic acid)and water(containing 0.1%formic acid)(gradient elution)at the flow rate of 0.4 mL/min.The column temperature was 40℃,and the sample size was 5μL.The ion source was electrospray ionization source,and the positive ion scanning was carried out in multiple reaction mode.The ion pairs for quantitative analysis were m/z 583.4→138.3(pyrrotinib)and m/z 494.5→393.4(internal standard),respectively.Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov.2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment.RESULTS:The linear range of pyrrotinib were 5-300 ng/mL(r=0.9993).The lower limit of quantification was 5 ng/mL.RSDs of intra-day and inter-day were not higher than 9.30%,and relative errors(REs)ranged-6.70%-5.04%.REs of stability tests were in the range of-1.92%-5.42%.The extraction method,matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested.The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL,with an average plasma concentration of 53.8 ng/mL;there was about 2.54 fold individual difference.CONCLUSIONS:Established LC-MS/MS method is simple,sensitive and accurate,and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.

关 键 词：吡咯替尼 液相色谱-串联质谱法 伊马替尼 乳腺癌 血药浓度监测 

分 类 号：R917[医药卫生—药物分析学]