Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters

Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of m...

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Main Authors: Jiapeng Li, Hao-Jie Zhu
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/11/2718
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author Jiapeng Li
Hao-Jie Zhu
author_facet Jiapeng Li
Hao-Jie Zhu
author_sort Jiapeng Li
collection DOAJ
description Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of many drug-metabolizing enzymes and transporters (DMETs) in tissues relevant to drug metabolism and disposition. Previous studies have consistently demonstrated marked interindividual variability in DMET protein expression, suggesting that varied DMET function is an important contributing factor for interindividual variability in pharmacokinetics (PK) and pharmacodynamics (PD) of medications. Moreover, differential DMET expression profiles were observed across different species and in vitro models. Therefore, caution must be exercised when extrapolating animal and in vitro DMET proteomics findings to humans. In recent years, DMET proteomics has been increasingly utilized for the development of physiologically based pharmacokinetic models, and DMET proteins have also been proposed as biomarkers for prediction of the PK and PD of the corresponding substrate drugs. In sum, despite the existence of many challenges in the analytical technology and data analysis methods of LC-MS/MS-based proteomics, DMET proteomics holds great potential to advance our understanding of PK behavior at the individual level and to optimize treatment regimens via the DMET protein biomarker-guided precision pharmacotherapy.
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spelling doaj.art-0d599f48bede46e78319098036864a3c2023-11-20T03:33:25ZengMDPI AGMolecules1420-30492020-06-012511271810.3390/molecules25112718Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and TransportersJiapeng Li0Hao-Jie Zhu1Department of Clinical Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USADepartment of Clinical Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USALiquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of many drug-metabolizing enzymes and transporters (DMETs) in tissues relevant to drug metabolism and disposition. Previous studies have consistently demonstrated marked interindividual variability in DMET protein expression, suggesting that varied DMET function is an important contributing factor for interindividual variability in pharmacokinetics (PK) and pharmacodynamics (PD) of medications. Moreover, differential DMET expression profiles were observed across different species and in vitro models. Therefore, caution must be exercised when extrapolating animal and in vitro DMET proteomics findings to humans. In recent years, DMET proteomics has been increasingly utilized for the development of physiologically based pharmacokinetic models, and DMET proteins have also been proposed as biomarkers for prediction of the PK and PD of the corresponding substrate drugs. In sum, despite the existence of many challenges in the analytical technology and data analysis methods of LC-MS/MS-based proteomics, DMET proteomics holds great potential to advance our understanding of PK behavior at the individual level and to optimize treatment regimens via the DMET protein biomarker-guided precision pharmacotherapy.https://www.mdpi.com/1420-3049/25/11/2718proteomicsLC-MS/MSdrug-metabolizing enzymestransporters
spellingShingle Jiapeng Li
Hao-Jie Zhu
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
Molecules
proteomics
LC-MS/MS
drug-metabolizing enzymes
transporters
title Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
title_full Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
title_fullStr Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
title_full_unstemmed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
title_short Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
title_sort liquid chromatography tandem mass spectrometry lc ms ms based proteomics of drug metabolizing enzymes and transporters
topic proteomics
LC-MS/MS
drug-metabolizing enzymes
transporters
url https://www.mdpi.com/1420-3049/25/11/2718
work_keys_str_mv AT jiapengli liquidchromatographytandemmassspectrometrylcmsmsbasedproteomicsofdrugmetabolizingenzymesandtransporters
AT haojiezhu liquidchromatographytandemmassspectrometrylcmsmsbasedproteomicsofdrugmetabolizingenzymesandtransporters