Inception and development of a LC-MS/MS assay for the multiplexed quantitation of nine human drug transporter biomarkers.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-03-01 Epub Date: 2024-02-20 DOI:10.4155/bio-2023-0197
Eugene P Kadar, Christopher L Holliman, Manoli Vourvahis, A David Rodrigues
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引用次数: 0

Abstract

Background: It has become common practice to assess solute carrier transporter (SLC)-mediated drug-drug interactions (DDIs) by quantitating various individual endogenous compounds as biomarkers in human plasma and urine. The goal of this work was to develop biomarker multiplex assays that could be utilized during first in human studies to support the simultaneous assessment of clinical DDI risk across various SLCs. Methodology: Hydrophilic interaction chromatography-MS/MS methods were developed, and validations were performed. Results: The multiplex assays were applied to a first in human study. Placebo/reference subject biomarker data were consistent with single assay in-house and published data. Conclusion: This work demonstrates the utility of these multiplex methods to support the concurrent evaluation of clinical DDI risk across various SLCs.

开始并开发一种 LC-MS/MS 分析方法,用于对九种人类药物转运生物标志物进行多重定量。
背景:通过量化人体血浆和尿液中作为生物标志物的各种单个内源性化合物来评估溶质载体转运体(SLC)介导的药物间相互作用(DDI)已成为一种常见做法。这项工作的目标是开发生物标志物多重检测方法,以便在首次人体研究中使用,支持同时评估各种 SLC 的临床 DDI 风险。方法:开发了亲水相互作用色谱-MS/MS 方法,并进行了验证。结果:多重检测方法首次应用于人体研究。安慰剂/参照受试者生物标志物数据与单项检测的内部数据和已发表数据一致。结论这项工作证明了这些多重方法在支持同时评估各种 SLC 的临床 DDI 风险方面的实用性。
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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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