Variability in Mass Spectrometry-based Quantification of Clinically Relevant 
Drug Transporters and Drug Metabolizing Enzymes

Wegler, Christine; Gaugaz, Fabienne Z.; Andersson, Tommy B.; Wisniewski, Jacek R.; Busch, Diana; Groeer, Christian; Oswald, Stefan; Noren, Agneta; Weiss, Frederik; Hammer, Helen S.; Joos, Thomas O.; Poetz, Oliver; Achour, Brahim; Rostami-Hodjegan, Amin; van de Steeg, Evita; Wortelboer, Heleen M.; Artursson, Per

doi:10.1021/acs.molpharmaceut.7b00364

Datensatz

DATENSATZ AKTIONENEXPORT

Zur Ablage hinzufügen

Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben

Zeitschriftenartikel

Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes

MPG-Autoren

/persons/resource/persons78895

Wisniewski, Jacek R.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

Externe Ressourcen

http://pubs.acs.org/doi/suppl/10.1021/acs.molpharmaceut.7b00364
(Ergänzendes Material)

Volltexte (beschränkter Zugriff)

Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.

Volltexte (frei zugänglich)

acs.molpharmaceut.7b00364.pdf
(Verlagsversion), 4MB

Ergänzendes Material (frei zugänglich)

Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar

Zitation

Wegler, C., Gaugaz, F. Z., Andersson, T. B., Wisniewski, J. R., Busch, D., Groeer, C., et al. (2017). Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes. Molecular Pharmaceutics, 14(9), 3142-3151. doi:10.1021/acs.molpharmaceut.7b00364.

Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002E-080A-4

Zusammenfassung

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 4 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.