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

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 duri...

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Bibliographic Details
Published in:Bioanalysis Vol. 16; no. 6; p. 347
Main Authors: Kadar, Eugene P, Holliman, Christopher L, Vourvahis, Manoli, Rodrigues, A David
Format: Journal Article
Language:English
Published: England 01.03.2024
Subjects:
Biomarkers
Chromatography, Liquid - methods
Drug Interactions
Humans
Liquid Chromatography-Mass Spectrometry
Membrane Transport Proteins
Tandem Mass Spectrometry - methods
biomarker
HILIC–MS/MS
drug–drug interactions
solute carrier transporter
ISSN:1757-6199, 1757-6199
Online Access:Get more information
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Summary: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. Hydrophilic interaction chromatography-MS/MS methods were developed, and validations were performed. 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. 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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ISSN:1757-6199
1757-6199
DOI:10.4155/bio-2023-0197