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...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-06-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/25/11/2718 |
_version_ | 1797565540942741504 |
---|---|
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. |
first_indexed | 2024-03-10T19:13:40Z |
format | Article |
id | doaj.art-0d599f48bede46e78319098036864a3c |
institution | Directory Open Access Journal |
issn | 1420-3049 |
language | English |
last_indexed | 2024-03-10T19:13:40Z |
publishDate | 2020-06-01 |
publisher | MDPI AG |
record_format | Article |
series | Molecules |
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 |