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

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis 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

引用次数: 0

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.