利用 LC-MS/MS 同时测定人体血浆中的瑞普替尼及其去甲基代谢物

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Zhou-Yi Qian, Ping Wang, Zi-Yi Wang, Yang Zhao, Tian-Tian Du, Hao Xu, Yong-Qing Wang, Lu-Ning Sun
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引用次数: 0

摘要

研究背景瑞普替尼是最近开发的一种具有开关控制能力的酪氨酸激酶抑制剂,可抑制KIT(KIT原癌基因受体酪氨酸激酶)和血小板衍生生长因子受体α(PDGFRA)突变体的原发性和继发性激活,而这些突变体是胃肠道间质瘤进展的诱因:本研究开发并验证了一种高效液相色谱-串联质谱法,用于测定人血浆中瑞瑞替尼及其活性去甲基代谢物DP-5439的浓度。血浆样品经提取后用含内标物的乙腈沉淀回收,并在分析前用乙腈稀释。采用Waters ACQUITY UPLC HSS T3色谱柱(2.1 mm × 50 mm,1.8 μm)分离瑞普替尼和DP-5439,流动相A为0.1%甲酸和5 mM甲酸铵水溶液,流动相B为乙腈,梯度洗脱:校准曲线在以下浓度范围内呈线性关系:结果:校准曲线在以下浓度范围内呈线性:瑞瑞替尼为 7.5 至 3000 纳克/毫升,DP-5439 为 10 至 4000 纳克/毫升。质控样品中所有分析物的日内和日间精确度约为15%。提取血浆样品中的相对基质效应(不同水平为 90.3%-108.8%)被认为是可以接受的:该方法将成为肿瘤学的有用工具,促进瑞瑞替尼的进一步临床开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS.

Background: Ripretinib, a recently developed tyrosine kinase inhibitor with switch-control abilities, can inhibit both primary and secondary activation of KIT(KIT proto-oncogene receptor tyrosine kinase) and platelet-derived growth factor receptor alpha (PDGFRA) mutants, which contribute to gastrointestinal stromal tumor progression.

Methods: In this study, a high-performance liquid chromatography-tandem mass spectrometry method to measure the concentrations of ripretinib and its active desmethyl metabolite DP-5439 in human plasma was developed and validated. Plasma samples were extracted and recovered by precipitation with acetonitrile containing the internal standard and diluted with acetonitrile before analysis. Ripretinib and DP-5439 were separated using chromatography on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 μm) with gradient elution using 0.1% formic acid and 5 mM ammonium formate in water as mobile phase A and acetonitrile as mobile phase B. The mobile phase was set to a flow rate of 0.5 mL/min.

Results: The calibration curves were linear across the following concentration range: 7.5 to 3000 ng/mL for ripretinib and 10 to 4000 ng/mL for DP-5439. The intraday and interday precisions were approximately 15% for all analytes in the quality control samples. The relative matrix effects in extracted plasma samples (90.3%-108.8% at different levels) were considered acceptable.

Conclusions: This method will be a useful tool in oncology to facilitate the further clinical development of ripretinib.

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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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