An LC-MS/MS method for determination of the bromodomain inhibitor ZEN-3694 and its metabolite ZEN-3791 in human plasma.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-01-01 Epub Date: 2024-03-18 DOI:10.4155/bio-2023-0252
Ye Feng, Haider Mahdi, Richard Piekarz, Jan H Beumer, Timothy W Synold
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Abstract

We have developed and validated a novel LC-MS/MS method for the simultaneous quantification of ZEN-3694 and its active metabolite ZEN-3791 in human plasma after protein precipitation. Stable isotope-labeled versions were used as internal standards. Chromatographic separation was achieved on a Kinetex C18 column using 0.1% formic acid in H2O and 0.1% formic acid in MeOH as mobile phases. Detection was performed via positive electrospray ionization mode with multiple reaction monitoring. The assay exhibited linearity in the concentration range of 5-5000 ng/ml for both analytes. Intra- and inter-assay precision and accuracy were within ±11%. ZEN-3694 and ZEN-3791 recoveries were between 93 and 105%. This LC-MS/MS assay is an essential tool to study ZEN-3694 in an ongoing clinical trial (NCT04840589).

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用 LC-MS/MS 方法测定人体血浆中的溴化酶抑制剂 ZEN-3694 及其代谢物 ZEN-3791。
我们开发并验证了一种新型的 LC-MS/MS 方法,用于同时定量蛋白质沉淀后人体血浆中的 ZEN-3694 及其活性代谢物 ZEN-3791。采用稳定同位素标记作为内标。色谱分离采用 Kinetex C18 色谱柱,以 0.1% 甲酸溶于 H2O 和 0.1% 甲酸溶于 MeOH 作为流动相。检测采用电喷雾正离子模式和多反应监测模式。两种分析物在 5-5000 纳克/毫升的浓度范围内呈线性关系。测定内和测定间的精密度和准确度均在±11%以内。ZEN-3694 和 ZEN-3791 的回收率在 93% 和 105% 之间。该 LC-MS/MS 分析法是正在进行的临床试验(NCT04840589)中研究 ZEN-3694 的重要工具。
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来源期刊
Accounts of Chemical Research
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.
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