Database of Optimized Proteomic Quantitative Methods for Human Drug Disposition-Related Proteins for Applications in Physiologically Based Pharmacokinetic Modeling.

Autor: Vrana M; Department of Pharmaceutics, University of Washington, Seattle, Washington, USA., Whittington D; Medicinal Chemistry, University of Washington, Seattle, Washington, USA., Nautiyal V; Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India., Prasad B; Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2017 Apr; Vol. 6 (4), pp. 267-276. Date of Electronic Publication: 2017 Apr 04.
DOI: 10.1002/psp4.12170
Abstrakt: The purpose of this study was to create an open access repository of validated liquid chromatography tandem mass spectrometry (LC-MS/MS) multiple reaction monitoring (MRM) methods for quantifying 284 important proteins associated with drug absorption, distribution, metabolism, and excretion (ADME). Various in silico and experimental approaches were used to select surrogate peptides and optimize instrument parameters for LC-MS/MS quantification of the selected proteins. The final methods were uploaded to an online public database (QPrOmics; www.qpromics.uw.edu/qpromics/assay/), which provides essential information for facile method development in triple quadrupole mass spectrometry (MS) instruments. To validate the utility of the methods, the differential tissue expression of 107 key ADME proteins was characterized in the tryptic digests of the pooled subcellular fractions of human liver, kidneys, intestines, and lungs. These methods and the data are critical for development of physiologically based pharmacokinetic (PBPK) models to predict xenobiotic disposition.
(© 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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