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

Bosilkovska Weisskopf, Marija; Deglon, Julien; Samer, Caroline Flora; Walder, Bernhard; Desmeules, Jules Alexandre; Staub, Christian; Daali, Youssef

doi:10.4155/bio.13.289

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Title		Simultaneous LC-MS/MS quantification of P-glycoprotein and cytochrome P450 probe substrates and their metabolites in DBS and plasma
Authors		Bosilkovska Weisskopf, Marija Deglon, Julien Samer, Caroline Flora Walder, Bernhard Desmeules, Jules Alexandre Staub, Christian Daali, Youssef
Published in		Bioanalysis. 2014, vol. 6, no. 2, p. 151-64
Abstract		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.
Keywords		Animals — Bupropion/blood/metabolism/pharmacokinetics — Caffeine/blood/metabolism/pharmacokinetics — Calibration — Chromatography, High Pressure Liquid/standards — Cytochrome P-450 Enzyme System/metabolism — Dextromethorphan/blood/metabolism/pharmacokinetics — Dried Blood Spot Testing — Flurbiprofen/blood/metabolism/pharmacokinetics — Half-Life — Male — Midazolam/blood/metabolism/pharmacokinetics — Omeprazole/blood/metabolism/pharmacokinetics — P-Glycoprotein/metabolism — Pharmaceutical Preparations/blood/metabolism — Substrate Specificity — Tandem Mass Spectrometry/standards — Terfenadine/analogs & derivatives/blood/metabolism/pharmacokinetics
Identifiers		DOI: 10.4155/bio.13.289 PMID: 24423593
Full text		Article (Published version) (1.3 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine légale
Research groups		Groupe Desmeules Jules (pharmacologie/toxicologie) (567) Pharmaco-omiques et médecine de précision (1003) Toxicologie analytique et forensique (120)
Citation (ISO format)		BOSILKOVSKA WEISSKOPF, Marija et al. Simultaneous LC-MS/MS quantification of P-glycoprotein and cytochrome P450 probe substrates and their metabolites in DBS and plasma. In: Bioanalysis, 2014, vol. 6, n° 2, p. 151-64. doi: 10.4155/bio.13.289 https://archive-ouverte.unige.ch/unige:43679