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.
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 M1--M5 have been identified, including three hydroxylated metabolites M1--M3, one N-oxide M4 and one uncommon aromatized N-oxide M5. Accurate mass data have been obtained in both full scan and MSn 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.
Chen
Guodong
G
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. guodong.chen@spcorp.com
Daaro
Ibrahim
I
Pramanik
Birendra N
BN
Piwinski
John J
JJ
D000818:Animals; D002853:Chromatography, Liquid; D003497:Cyclic N-Oxides / Q000032:analysis / Q000378:metabolism; D039563:Histamine H1 Antagonists, Non-Sedating / Q000032:analysis* / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D017336:Loratadine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D008861:Microsomes / Q000737:chemistry; D051381:Rats; D012680:Sensitivity and Specificity
D003497:Cyclic N-Oxides; D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine; C121345:desloratadine