Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes.
Mol Pharm
; 14(9): 3142-3151, 2017 09 05.
Article
em En
| MEDLINE
| ID: mdl-28767254
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 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espectrometria de Massas
/
Proteômica
/
Proteínas de Membrana
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article