Simultaneous LC-MS/MS quantification of P-glycoprotein and cytochrome P450 probe substrates and their metabolites in DBS and plasma.

Details

Serval ID
serval:BIB_0937F03C2987
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Simultaneous LC-MS/MS quantification of P-glycoprotein and cytochrome P450 probe substrates and their metabolites in DBS and plasma.
Journal
Bioanalysis
Author(s)
Bosilkovska M., Déglon J., Samer C., Walder B., Desmeules J., Staub C., Daali Y.
ISSN
1757-6199 (Electronic)
ISSN-L
1757-6180
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
6
Number
2
Pages
151-164
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
BACKGROUND: An LC-MS/MS method has been developed for the simultaneous quantification of P-glycoprotein (P-gp) and cytochrome P450 (CYP) probe substrates and their Phase I metabolites in DBS and plasma. P-gp (fexofenadine) and CYP-specific substrates (caffeine for CYP1A2, bupropion for CYP2B6, flurbiprofen for CYP2C9, omeprazole for CYP2C19, dextromethorphan for CYP2D6 and midazolam for CYP3A4) and their metabolites were extracted from DBS (10 µl) using methanol. Analytes were separated on a reversed-phase LC column followed by SRM detection within a 6 min run time.
RESULTS: The method was fully validated over the expected clinical concentration range for all substances tested, in both DBS and plasma. The method has been successfully applied to a PK study where healthy male volunteers received a low dose cocktail of the here described P-gp and CYP probes. Good correlation was observed between capillary DBS and venous plasma drug concentrations.
CONCLUSION: Due to its low-invasiveness, simple sample collection and minimal sample preparation, DBS represents a suitable method to simultaneously monitor in vivo activities of P-gp and CYP.
Keywords
Animals, Bupropion/blood, Bupropion/metabolism, Caffeine/blood, Caffeine/metabolism, Calibration, Chromatography, High Pressure Liquid/standards, Cytochrome P-450 Enzyme System/metabolism, Dextromethorphan/blood, Dextromethorphan/metabolism, Dried Blood Spot Testing, Flurbiprofen/blood, Flurbiprofen/metabolism, Half-Life, Male, Midazolam/blood, Midazolam/metabolism, Omeprazole/blood, Omeprazole/metabolism, P-Glycoprotein/metabolism, Pharmaceutical Preparations/blood, Pharmaceutical Preparations/metabolism, Substrate Specificity, Tandem Mass Spectrometry/standards, Terfenadine/analogs & derivatives, Terfenadine/blood
Pubmed
Web of science
Create date
09/02/2015 10:07
Last modification date
20/08/2019 12:31
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