Titre
Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry: Application to the analysis of drug-drug interaction.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Liu, Y.
Auteure/Auteur
Jann, M.
Auteure/Auteur
Vandenberg, C.
Auteure/Auteur
Eap, C.B.
Auteure/Auteur
Shamsi, S.A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1873-3778
Statut éditorial
Publié
Date de publication
2015
Volume
1420
Première page
119
Dernière page/numéro d’article
128
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
To-date, there has been no effective chiral capillary electrophoresis-mass spectrometry (CE-MS) method reported for the simultaneous enantioseparation of the antidepressant drug, venlafaxine (VX) and its structurally-similar major metabolite, O-desmethylvenlafaxine (O-DVX). This is mainly due to the difficulty of identifying MS compatible chiral selector, which could provide both high enantioselectivity and sensitive MS detection. In this work, poly-sodium N-undecenoyl-L,L-leucylalaninate (poly-L,L-SULA) was employed as a chiral selector after screening several dipeptide polymeric chiral surfactants. Baseline separation of both O-DVX and VX enantiomers was achieved in 15 min after optimizing the buffer pH, poly-L,L-SULA concentration, nebulizer pressure and separation voltage. Calibration curves in spiked plasma (recoveries higher than 80%) were linear over the concentration range 150-5000 ng/mL for both VX and O-DVX. The limit of detection (LOD) was found to be as low as 30 ng/mL and 21 ng/mL for O-DVX and VX, respectively. This method was successfully applied to measure the plasma concentrations of human volunteers receiving VX or O-DVX orally when co-administered without and with indinivar therapy. The results suggest that micellar electrokinetic chromatography electrospray ionization-tandem mass spectrometry (MEKC-ESI-MS/MS) is an effective low cost alternative technique for the pharmacokinetics and pharmacodynamics studies of both O-DVX and VX enantiomers. The technique has potential to identify drug-drug interaction involving VX and O-DVX enantiomers while administering indinivar therapy.
Sujets
PID Serval
serval:BIB_6C79E913C6C8
PMID
Date de création
2015-10-30T12:29:16.952Z
Date de création dans IRIS
2025-05-20T21:56:28Z