Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes

Research output: Contribution to journalArticle

  • External authors:
  • Christine Wegler
  • Fabienne Z Gaugaz
  • Tommy B Andersson
  • Jacek R Wiśniewski
  • Diana Busch
  • Christian Gröer
  • Stefan Oswald
  • Frederik Weiss
  • Helen Hammer
  • Thomas O Joos
  • Oliver Poetz
  • Evita van de Steeg
  • Heleen M. Wortelboer
  • Per Artursson

Abstract

Many different methods are used for mass-spectrometry based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically relevant drug transporters and metabolizing enzymes in human liver. Mean protein concentrations were in general quantified to similar levels by methods using whole tissue lysates. Methods using subcellular membrane fractionation gave incomplete enrichment of the proteins. When the enriched proteins were adjusted to levels in whole tissue lysates, they were on average four-fold lower than those quantified directly in whole tissue lysates. The differences in protein levels were propagated into differences in predictions of hepatic clearance. In conclusion, caution is needed when comparing and applying quantitative proteomics data obtained with different methods, especially since membrane fractionation is common practice for protein quantification used in drug clearance predictions.

Bibliographical metadata

Original languageEnglish
Pages (from-to)3142-3151
Number of pages10
JournalMolecular Pharmaceutics
Volume14
Issue number9
Early online date2 Aug 2017
DOIs
Publication statusPublished - 2017

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