General unknown screening procedure for the characterization of human drug metabolites: application to loratadine phase I metabolism.

Détails

ID Serval
serval:BIB_C13247A9E144
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
General unknown screening procedure for the characterization of human drug metabolites: application to loratadine phase I metabolism.
Périodique
Journal of separation science
Auteur(s)
Picard N., Dridi D., Sauvage F.L., Boughattas N.A., Marquet P.
ISSN
1615-9314[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
32
Numéro
13
Pages
2209-17
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
This article describes the application of a recently developed general unknown screening (GUS) strategy based on LC coupled to a hybrid linear IT-triple quadrupole mass spectrometer (LC-MS/MS-LIT) for the simultaneous detection and identification of drug metabolites following in vitro incubation with human liver microsomes. The histamine H1 receptor antagonist loratadine was chosen as a model compound to demonstrate the interest of such approach, because of its previously described complex and extensive metabolism. Detection and mass spectral characterization were based on data-dependent acquisition, switching between a survey scan acquired in the ion-trapping Q3 scan mode with dynamic subtraction of background noise, and a dependent scan in the ion-trapping product ion scan mode of automatically selected parent ions. In addition, the MS(3) mode was used in a second step to confirm the structure of a few fragment ions. The sensitivity of the ion-trapping modes combined with the selectivity of the triple quadrupole modes allowed, with only one injection, the detection and identification of 17 phase I metabolites of loratadine. The GUS procedure used in this study may be applicable as a generic technique for the characterization of drug metabolites after in vitro incubation, as well as probably in vivo experiments.
Pubmed
Web of science
Création de la notice
09/07/2009 13:34
Dernière modification de la notice
20/08/2019 15:35
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