title: Use of on-line hydrogen/deuterium exchange to facilitate metabolite identification.
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.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, RY80L-109, P.O. Box 2000, Rahway, NJ 07065, USA. david_liu@merck.com
authors.forename: D Q
authors.initials: DQ
authors.lastname: Liu
authors.forename: C E
authors.initials: CE
authors.lastname: Hop
authors.forename: M G
authors.initials: MG
authors.lastname: Beconi
authors.forename: A
authors.initials: A
authors.lastname: Mao
authors.forename: S H
authors.initials: SH
authors.lastname: Chiu
mesh_terms: D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003903:Deuterium; D017666:Deuterium Oxide; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005960:Glucosides / Q000032:analysis*; D005966:Glucuronidase; D020719:Glucuronides / Q000032:analysis*; D006859:Hydrogen; D007202:Indicators and Reagents; D013058:Mass Spectrometry / Q000379:methods; D013450:Sulfones / Q000032:analysis*; D013454:Sulfoxides / Q000032:analysis*; D014867:Water
chemical_list: D000577:Amides; D005960:Glucosides; D020719:Glucuronides; D007202:Indicators and Reagents; D013450:Sulfones; D013454:Sulfoxides; D014867:Water; D006859:Hydrogen; D003903:Deuterium; D005966:Glucuronidase; D017666:Deuterium Oxide