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

  • 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

Standard

Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes. / Wegler, Christine; Gaugaz, Fabienne Z; Andersson, Tommy B; Wiśniewski, Jacek R; Busch, Diana; Gröer, Christian; Oswald, Stefan; Weiss, Frederik; Hammer, Helen; Joos, Thomas O; Poetz, Oliver; Achour, Brahim; Rostami-Hochaghan, Amin; Steeg, Evita van de; Wortelboer, Heleen M.; Artursson, Per.

In: Molecular Pharmaceutics, Vol. 14, No. 9, 2017, p. 3142-3151.

Research output: Contribution to journalArticle

Harvard

Wegler, C, Gaugaz, FZ, Andersson, TB, Wiśniewski, JR, Busch, D, Gröer, C, Oswald, S, Weiss, F, Hammer, H, Joos, TO, Poetz, O, Achour, B, Rostami-Hochaghan, A, Steeg, EVD, Wortelboer, HM & Artursson, P 2017, 'Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes', Molecular Pharmaceutics, vol. 14, no. 9, pp. 3142-3151. https://doi.org/10.1021/acs.molpharmaceut.7b00364

APA

Wegler, C., Gaugaz, F. Z., Andersson, T. B., Wiśniewski, J. R., Busch, D., Gröer, C., ... Artursson, P. (2017). Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes. Molecular Pharmaceutics, 14(9), 3142-3151. https://doi.org/10.1021/acs.molpharmaceut.7b00364

Vancouver

Wegler C, Gaugaz FZ, Andersson TB, Wiśniewski JR, Busch D, Gröer C et al. Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes. Molecular Pharmaceutics. 2017;14(9):3142-3151. https://doi.org/10.1021/acs.molpharmaceut.7b00364

Author

Wegler, Christine ; Gaugaz, Fabienne Z ; Andersson, Tommy B ; Wiśniewski, Jacek R ; Busch, Diana ; Gröer, Christian ; Oswald, Stefan ; Weiss, Frederik ; Hammer, Helen ; Joos, Thomas O ; Poetz, Oliver ; Achour, Brahim ; Rostami-Hochaghan, Amin ; Steeg, Evita van de ; Wortelboer, Heleen M. ; Artursson, Per. / Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes. In: Molecular Pharmaceutics. 2017 ; Vol. 14, No. 9. pp. 3142-3151.

Bibtex

@article{96d13ec358574a499b3ab74ff452638f,
title = "Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes",
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.",
author = "Christine Wegler and Gaugaz, {Fabienne Z} and Andersson, {Tommy B} and Wiśniewski, {Jacek R} and Diana Busch and Christian Gr{\"o}er and Stefan Oswald and Frederik Weiss and Helen Hammer and Joos, {Thomas O} and Oliver Poetz and Brahim Achour and Amin Rostami-Hochaghan and Steeg, {Evita van de} and Wortelboer, {Heleen M.} and Per Artursson",
year = "2017",
doi = "10.1021/acs.molpharmaceut.7b00364",
language = "English",
volume = "14",
pages = "3142--3151",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "9",

}

RIS

TY - JOUR

T1 - Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes

AU - Wegler, Christine

AU - Gaugaz, Fabienne Z

AU - Andersson, Tommy B

AU - Wiśniewski, Jacek R

AU - Busch, Diana

AU - Gröer, Christian

AU - Oswald, Stefan

AU - Weiss, Frederik

AU - Hammer, Helen

AU - Joos, Thomas O

AU - Poetz, Oliver

AU - Achour, Brahim

AU - Rostami-Hochaghan, Amin

AU - Steeg, Evita van de

AU - Wortelboer, Heleen M.

AU - Artursson, Per

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1021/acs.molpharmaceut.7b00364

DO - 10.1021/acs.molpharmaceut.7b00364

M3 - Article

VL - 14

SP - 3142

EP - 3151

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 9

ER -