Article: article from journal or magazin.
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.
Journal of Chromatography. A
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Calibration, Chromatography, Micellar Electrokinetic Capillary/methods, Desvenlafaxine Succinate/blood, Desvenlafaxine Succinate/isolation & purification, Drug Interactions, Electrophoresis, Capillary/methods, HIV/physiology, HIV Infections/blood, HIV Infections/drug therapy, HIV Protease Inhibitors/therapeutic use, Humans, Indinavir/therapeutic use, Limit of Detection, Polymers/chemistry, Spectrometry, Mass, Electrospray Ionization/methods, Stereoisomerism, Tandem Mass Spectrometry/methods, Venlafaxine Hydrochloride/blood, Venlafaxine Hydrochloride/isolation & purification
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