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

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis 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

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.

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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。

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.