title: Rapid analysis of isomeric exogenous metabolites by differential mobility spectrometry-mass spectrometry.
abstract: The direct separation of isomeric glucuronide metabolites from propranolol dosed tissue extracts by differential mobility spectrometry-mass spectrometry (DMS-MS) with the use of the polar gas-phase chemical modifier acetonitrile was demonstrated. The DMS gas-phase separation was able to resolve the isomeric metabolites with separation times on the order of milliseconds instead of minutes which is typically required when using pre-ionization chromatographic separation methods. Direct separation of isomeric metabolites from the complex tissue extract was confirmed by implementing a high-performance liquid chromatography (HPLC) separation prior to the DMS-MS analysis to pre-separate the species of interest. The ability to separate isomeric exogenous metabolites directly from a complex tissue extract is expected to facilitate the drug development process by increasing analytical throughput without the requirement for pre-ionization cleanup or separation strategies.
authors: Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6131, USA.
authors: Whitney B
authors: WB
authors: Parson
authors: Bradley B
authors: BB
authors: Schneider
authors: Vilmos
authors: V
authors: Kertesz
authors: Jay J
authors: JJ
authors: Corr
authors: Thomas R
authors: TR
authors: Covey
authors: Gary J
authors: GJ
authors: Van Berkel
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D055808:Drug Discovery / Q000379:methods*; D020719:Glucuronides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D006651:Histocytochemistry / Q000379:methods*; D007536:Isomerism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D011433:Propranolol / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D020719:Glucuronides; D011433:Propranolol