Work

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

Year: 2017

Type: article

Abstract: 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.

Source: CPT Pharmacometrics & Systems Pharmacology

DOI: 10.1002/psp4.12170

Authors: M Vrana, D Whittington, V Nautiyal, B Prasad

Institutions: University of Washington, Indian Institute of Technology Kharagpur

Language: English

Topic: Advanced Proteomics Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,140