Database of optimized proteomic quantitative methods for human drug disposition-related proteins for applications in physiologically based pharmacokinetic modeling
Open accessAbstract
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.
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A previously reported database proposed surrogate peptides and LC-MS/MS parameters for NAT1 and NAT2 but did not provide quantitative data.
“A previously reported database of proteins for quantitative analysis proposed surrogate peptides and LC-MS/MS parameters for NAT1 and NAT2, but did not provide any quantitative data.51”
From N-Acetyltransferase (NAT) 1 and NAT2 Enzyme Activities Drive Interindividual Variability in Sulfamethoxazole N-Acetylation (2025) · cites this paper as [51]
The Methods (Surrogate peptide selection; page unavailable) describe selecting surrogate peptides and generating MS settings, and the Results (QPrOmics workflow; page unavailable) list peptide sequences and LC-MS/MS parameters as database outputs. But the claim that the paper provided no quantitative data is too broad: the Results (Differential tissue expression of drug metabolizing enzymes; page unavailable) report measured expression and relative inter-tissue variability. The available results do not establish whether expression values were provided specifically for NAT1 or NAT2. (LLM, conf=0.87)
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Lanphier, R. M., Latham, B. D., Gerringer, A. J., Interrante, T., Jones, C. D., De Buysscher, T., Fallon, J. K., & Jackson, K. D. (2025) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2025.100195 · Cited by 1 · see citing works
- Authors
- Vrana, M., Whittington, D., Nautiyal, V, & Prasad, B.
- Affiliations
- University of Washington (US)
- Indian Institute of Technology Kharagpur (IN)
- Corresponding author
- Prasad, B
- ORCID
- Venue
- CPT: Pharmacometrics & Systems Pharmacology
- Publisher
- Wiley
- Published
- 2017-04
- Volume
- 6
- Issue
- 4
- Pages
- 267-276
- ISSN
- 2163-8306 (ISSN-L)
- PMC
- PMC5397556
- OpenAlex
- W2574406311
- Cited by
- 22
- References
- 37
- Citations by year
- 2025: 2 · 2024: 1 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 4
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- NIH (R01HD081299)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- multiple reaction monitoring, LC-MS/MS method optimization, physiologically based pharmacokinetic modeling, xenobiotic disposition, tissue expression, method validation
- MeSH terms
- Chromatography, Liquid, Humans, Intestinal Mucosa, Intestines, Kidney, Liver, Lung, Models, Theoretical, Pharmacokinetics, Proteome, Databases, Protein, Proteomics, Tandem Mass Spectrometry, Drug Repositioning
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