A validated high‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous determination of irinotecan and two major metabolites in rat plasma: Application for the pharmacokinetics study

IF 17.7 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-05-10 DOI:10.1002/sscp.202400069

Liangzhu Jiang, Gu Nan, Peng Yuzhi, Liao Yuxin, Zhou Limin, Yongbing Sun

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Abstract

A high‐performance liquid chromatography‐tandem mass spectrometry method has been developed for the determination of irinotecan, 7‐ethyl‐10‐hydroxycamptothecin (SN38), and SN38 glucuronide (SN38G) in rat plasma in the present study. The analytes were separated on a C18 column and a triple‐quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. Irinotecan, SN38 and SN38G could be well retained in the C18 column after optimization of mobile phase. A simple protein precipitation was used to pretreat the plasma. The extraction recovery was above 90% and the matrix effect could be negligible. The method was linear over the concentration ranges of 3.46–3458.8 ng/mL for irinotecan, 2.53–2530.0 ng/mL for SN38 and 2.5–2500.0 ng/mL for SN38G. The precision and accuracy was within the acceptable limits. The simple and convenient method was validated and successfully applied to support the pharmacokinetic study and elucidate the mechanism of irinotecan‐induced diarrhea after irinotecan was intravenously injected to the Sprague‐Dawley rats.

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同时测定大鼠血浆中伊立替康和两种主要代谢物的高效液相色谱-串联质谱法：在药代动力学研究中的应用

本研究建立了大鼠血浆中伊立替康、7-乙基-10-羟基喜树碱（SN38）和SN38葡萄糖醛酸苷（SN38G）的高效液相色谱-串联质谱检测方法。大鼠血浆中的伊立替康、7-乙基-10-羟基喜树碱（SN38）和 SN38 葡萄糖醛酸（SN38G）经 C18 色谱柱分离后，采用配备电喷雾离子源的三重四极杆质谱进行检测。优化流动相后，伊立替康、SN38和SN38G在C18柱中保留良好。对血浆进行了简单的蛋白质沉淀预处理。萃取回收率高于90%，基质效应可忽略不计。该方法在伊立替康（3.46-3458.8 ng/mL）、SN38（2.53-2530.0 ng/mL）和SN38G（2.5-2500.0 ng/mL）浓度范围内线性关系良好。精密度和准确度均在可接受范围内。该方法简便易行，可用于大鼠静脉注射伊立替康后的药代动力学研究和伊立替康诱导腹泻的机制研究。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.