Use of on-line hydrogen/deuterium exchange to facilitate metabolite identification |
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Authors: | Liu D Q Hop C E Beconi M G Mao A Chiu S H |
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Affiliation: | Department of Drug Metabolism, Merck Research Laboratories, RY80L-109, P.O. Box 2000, Rahway, NJ 07065, USA. david_liu@merck.com |
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Abstract: | 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. |
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