Rapid analysis of isomeric exogenous metabolites by differential mobility spectrometry - mass spectrometry

• Published in: Rapid communications in mass spectrometry Vol. 25; no. 22; pp. 3382 - 3386
• Main Authors: Parson, Whitney B., Schneider, Bradley B., Kertesz, Vilmos, Corr, Jay J., Covey, Thomas R., Van Berkel, Gary J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 30-11-2011
• Subjects: Acetonitrile; Animals; Chromatography, High Pressure Liquid; Drug Discovery - methods; Glucuronides - analysis; Glucuronides - chemistry; Glucuronides - metabolism; Histocytochemistry - methods; Isomerism; Liver - chemistry; Liver - metabolism; Male; Mass spectrometry; Mathematical analysis; Metabolites; Mice; Propranolol - pharmacokinetics; Separation; Spectrometry; Spectroscopy; Strategy; Tandem Mass Spectrometry - methods
• ISSN: 0951-4198; 1097-0231; 1097-0231
• DOI: 10.1002/rcm.5238

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. Published in 2011 by John Wiley & Sons, Ltd.