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Structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine using LTQ‐Orbitrap hybrid mass spectrometer in combination with online hydrogen/deuterium exchange HR‐LC/MS
Author(s) -
Chen Guodong,
Daaro Ibrahim,
Pramanik Birendra N.,
Piwinski John J.
Publication year - 2009
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1498
Subject(s) - chemistry , orbitrap , desloratadine , hydrogen–deuterium exchange , metabolite , mass spectrometry , chromatography , in vitro , microsome , tandem mass spectrometry , deuterium , pharmacology , biochemistry , medicine , physics , quantum mechanics
In vitro drug metabolism study is an integral part of drug discovery process. In this report, we have described the application of LTQ‐Orbitrap hybrid mass spectrometer in conjunction with online hydrogen (H)/deuterium (D) exchange high resolution (HR)‐LC/MS for structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine. Five metabolites M1M5 have been identified, including three hydroxylated metabolites M1M3, one N‐oxide M4 and one uncommon aromatized N‐oxide M5. Accurate mass data have been obtained in both full scan and MS n mode support assignments of metabolite structures with reported mass errors less than 3 ppm. Online H/D exchange HR‐LC/MS experiments provide additional evidence in differentiating hydroxylated metabolites from N‐oxides. This study demonstrates the effectiveness of this approach in structural characterization of drug metabolites. Copyright © 2008 John Wiley & Sons, Ltd.