title: High-throughput quantitative and qualitative analysis of microsomal incubations by cocktail analysis with an ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometer system.
abstract: BACKGROUND
  Metabolite identification studies are very resource intensive and also are rarely performed in early discovery. Here, we report the validation of an ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) platform for generating high-throughput stability data with structure elucidation in a single injection.
  
  
  METHODS
  Tandem mass spectrometry spectra were obtained for quantitative analysis using a generic information-dependent acquisition method from pooled microsomal samples incubated at low compound concentrations.
  
  
  RESULTS
  A good correlation was observed between clearance determined using UPLC-HRMS and UPLC-triple-quadrupole analysis. Structural elucidation performed with MassMetaSite™ (Molecular Discovery, Perugia, Italy) software identified 85% of the major metabolites of eight marketed drugs and over 100 internal compounds under these conditions.
  
  
  CONCLUSIONS
  For the first time, a high-throughput quantitative-qualitative workflow was established using a cocktail approach for sample analysis with UPLC-HRMS in order to enable metabolite identification in early discovery projects.
authors.affiliation: AbbVie Deutschland GmbH Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Backfisch
authors.forename: Beate
authors.initials: B
authors.lastname: Reder-Hilz
authors.forename: Juliane
authors.initials: J
authors.lastname: Hoeckels-Messemer
authors.forename: Jonas
authors.initials: J
authors.lastname: Angstenberger
authors.forename: Jens
authors.initials: J
authors.lastname: Sydor
authors.forename: Loic
authors.initials: L
authors.lastname: Laplanche
authors.forename: Michael
authors.initials: M
authors.lastname: Schulz
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D012984:Software