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Use of on‐line hydrogen/deuterium exchange to facilitate metabolite identification
Author(s) -
Liu David Q.,
Hop Cornelis E.C.A.,
Beconi María G.,
Mao Ann,
Chiu ShuetHing Lee
Publication year - 2001
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.442
Subject(s) - chemistry , metabolite , hydroxylation , hydrogen–deuterium exchange , mass spectrometry , biotransformation , chromatography , deuterium , glucuronide , organic chemistry , biochemistry , enzyme , physics , quantum mechanics
An Erratum for this article has been published in Rapid Communications in Mass Spectrometry 17(3) 2003, 264 Biotransformation studies performed on an investigational compound (I, represented by R1‐CH(NH 2 )‐CO‐N(R2)‐CH 2 ‐S‐R3) led to the identification of five metabolites (M1–M5). Based on LC/MS (liquid chromatography/mass spectrometry) analysis which included the use of H 2 O and D 2 O in the mobile phases, they were identified as the sulfoxide (M1), sulfone (M2), carbamoyl glucuronide (M3), N‐glucuronide (M4), and N‐glucoside (M5) metabolites, respectively. The structure of M3, a less commonly seen carbamoyl glucuronide metabolite, was established using on‐line H/D (hydrogen/deuterium) exchange experiments conducted by LC/MS. H/D exchange experiments were also used to distinguish the S‐oxidation structures of M1 and M2 from hydroxylation. Herein, the application of deuterium oxide as the LC/MS mobile phase for structural elucidation of drug metabolites in biological matrices is demonstrated. Copyright © 2001 John Wiley & Sons, Ltd.