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

Autor: Marija Bosilkovska, Julien Déglon, Caroline Samer, Bernhard Walder, Jules Desmeules, Christian Staub, Youssef Daali
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
CYP2B6
Clinical Biochemistry
Flurbiprofen
Pharmacology
Chromatography
High Pressure Liquid/standards
Dextromethorphan
Midazolam/blood/metabolism/pharmacokinetics
Analytical Chemistry
Substrate Specificity
Terfenadine/analogs & derivatives/blood/metabolism/pharmacokinetics
Cytochrome P-450 Enzyme System
Tandem Mass Spectrometry
Caffeine/blood/metabolism/pharmacokinetics
Sample preparation
P-Glycoprotein/metabolism
Pharmaceutical Preparations/blood/metabolism
General Pharmacology
Toxicology and Pharmaceutics
Chromatography
High Pressure Liquid
ddc:617
Chemistry
Venous Plasma
General Medicine
Medical Laboratory Technology
Tandem Mass Spectrometry/standards
Pharmaceutical Preparations
Calibration
Terfenadine
Omeprazole
medicine.drug
Half-Life
Analyte
Cytochrome P-450 Enzyme System/metabolism
Midazolam
In vivo
Caffeine
medicine
Animals
Dextromethorphan/blood/metabolism/pharmacokinetics
Bupropion/blood/metabolism/pharmacokinetics
ATP Binding Cassette Transporter
Subfamily B
Member 1
Bupropion
Chromatography
ddc:614.1
Flurbiprofen/blood/metabolism/pharmacokinetics
CYP1A2
Omeprazole/blood/metabolism/pharmacokinetics
Dried Blood Spot Testing
Zdroj: Bioanalysis, Vol. 6, No 2 (2014) pp. 151-64
ISSN: 1757-6199
Popis: 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.
Databáze: OpenAIRE
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