Database of Optimized Proteomic Quantitative Methods for Human Drug Disposition-Related Proteins for Applications in Physiologically Based Pharmacokinetic Modeling
| Autor: | D Whittington, Bhagwat Prasad, Marc Vrana, Vivek Nautiyal |
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| Rok vydání: | 2017 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Database Chemistry Selected reaction monitoring Kidney metabolism computer.software_genre Proteomics Tandem mass spectrometry 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Liquid chromatography–mass spectrometry 030220 oncology & carcinogenesis Modeling and Simulation Proteome Pharmacology (medical) computer ADME |
| Zdroj: | CPT: Pharmacometrics & Systems Pharmacology. 6:267-276 |
| ISSN: | 2163-8306 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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