title: 'All-in-one' analysis for metabolite identification using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry with collision energy switching.
abstract: The removal of bottlenecks in discovery stage metabolite identification studies is an ongoing challenge for the pharmaceutical industry. We describe the use of an 'All-in-One' approach to metabolite characterization that leverages the fast scanning and high mass accuracy of hybrid quadrupole time-of-flight mass spectrometry (QqToFMS) instruments. Full-scan MS and MS/MS data is acquired using collision energy switching without the preselection, either manually or in a data-dependent manner, of precursor ions. The acquisition of 'clean' MS/MS data is assisted by the use of ultrahigh-performance chromatography. Data acquired using this method can then be mined post-acquisition in a number of ways. These include using narrow window extracted ion chromatograms (nwXICs) for expected biotransformations, XICs for the product ions of the parent compound and/or expected modification of these product ions, and neutral loss chromatograms. This approach has the potential to be truly comprehensive for the determination of in vitro biotransformations in a drug discovery environment.
authors.affiliation: Merck Frosst Canada Ltd., 16711 Trans Canada Hwy. Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Wrona
authors.forename: Timo
authors.initials: T
authors.lastname: Mauriala
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bateman
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mortishire-Smith
authors.forename: Desmond
authors.initials: D
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D014700:Verapamil / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014700:Verapamil