title: MSE with mass defect filtering for in vitro and in vivo metabolite identification.
abstract: Metabolite identification studies involve the detection and structural characterization of the biotransformation products of drug candidates. These experiments are necessary throughout the drug discovery and development process. The use of high-resolution chromatography and high-resolution mass spectrometry together with data processing using mass defect filtering is described for in vitro and in vivo metabolite identification studies. Data collection was done using UPLC coupled with an orthogonal hybrid quadrupole time-of-flight mass spectrometer. This experimental approach enabled the use of MS(E) data collection (where E represents collision energy) which has previously been shown to be a powerful approach for metabolite identification studies. Post-acquisition processing with a prototype mass defect filtering program was used to eliminate endogenous interferences in the study samples, greatly enhancing the discovery of metabolites. The ease of this approach is illustrated by results showing the detection and structural characterization of metabolites in plasma from a preclinical rat pharmacokinetic study.
authors: Merck Frosst Canada Ltd., 16711 Trans Canada Hwy. Kirkland, Quebec, H9H 3L1, Canada. Kevin_Bateman@merck.com
authors: Kevin P
authors: KP
authors: Bateman
authors: Jose
authors: J
authors: Castro-Perez
authors: Mark
authors: M
authors: Wrona
authors: John P
authors: JP
authors: Shockcor
authors: Kate
authors: K
authors: Yu
authors: Renata
authors: R
authors: Oballa
authors: Deborah A
authors: DA
authors: Nicoll-Griffith
mesh_terms: D000818:Animals; D001711:Biotransformation; D004353:Drug Evaluation, Preclinical; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir