篇名: LC-MS/MS法测定人血浆中吡咯替尼的浓度及其临床应用
TITLE: Determination of Pyrrotinib Concentration in Human Plasma by LC-MS/MS and Its Clinical Application
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UltimateAQ-C18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0.4mL/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/z583.4→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5~300ng/mL(r=0.9993),定量下限为5ng/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32.6~82.8ng/mL,平均血药浓度为53.8ng/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。
ABSTRACT: 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 5 µL. 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=0.999 3). 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.
期刊: 2021年第32卷第22期
作者: 赵振寰,荆伟丽,刘涛,吕志强,曹志红,徐文
AUTHORS: ZHAO Zhenhuan ,JING Weili,LIU Tao,LYU Zhiqiang ,CAO Zhihong ,XU Wen
关键字: 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
KEYWORDS: Pyrrotinib;LC-MS/MS;Imatinib;Breast cancer ;Plasma concentration monitoring
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