Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Li J

PROVIDER: S-EPMC7321193 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Li Jiapeng J Zhu Hao-Jie HJ

Molecules (Basel, Switzerland) 20200611 11

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 DME ...[more]

PMID: 32545386

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Project description:Monitoring of marine mammal steroid hormone status using matrices alternative to blood is desirable due to the ability to remotely collect samples, which minimizes stress to the animal. However, measurement techniques in alternative matrices such as blubber described to date are limited in the number and types of hormones measured. Therefore, a new method using bead homogenization to QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction, C18 post extraction cleanup and analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and applied to the measurement of hormone suites in bottlenose dolphin blubber. Validations were conducted in blubber from fresh dead stranded bottlenose dolphin. The final method consisting of two LC separations and garnet bead homogenization was tested for extraction efficiencies. Steroids were separated using a biphenyl column for reproductive hormones and C18 column for corticosteroids. Three hormones previously noted in blubber, testosterone, progesterone, and cortisol, were quantified in addition to previously unmeasured androstenedione, 17-hydroxyprogesterone, 11-deoxycortisol, 11-deoxycorticosterone, and cortisone in a single sample (0.4 g blubber). Extraction efficiencies of all hormones from blubber ranged from 84% to 112% and all RSDs were comparable to those reported using immunoassay methods (< 15%). The method was successfully applied to remote biopsied blubber samples to measure baseline hormone concentrations. Through this method, increased coverage of steroid hormone pathways from a single remotely collected sample potentially enhances the ability to interpret biological phenomena such as reproduction and stress in wild dolphin populations. Graphical abstract The steroid hormone profile is quantifiable from a single sample of bottlenose dolphin blubber using liquid chromatography tandem mass spectrometry. This profile can be applied to remotely collected dart biopsies and be used to determine reproductive or stress status of a wild-living dolphin.

Dataset Information

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

Publications

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

Similar Datasets

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