title: Structural analysis of quazepam metabolites in bile by ion trap time-of-flight mass spectrometry.
abstract: Quazepam (QZP) is a long-acting benzodiazepine-type hypnotic. We searched for novel QZP metabolites in bile and determined their structures by liquid chromatography-ion trap time-of-flight mass spectrometry (LC-IT-TOF MS). The metabolites were extracted with ethyl acetate after β-glucuronidase treatment. First, a single MS spectrum was acquired. Second, MS(n) spectra were acquired for peaks that consisted of ions with the isotope pattern corresponding to molecules bearing one chlorine atom. The novel QZP metabolites found in this study were hydroxyquazepam, hydroxy-methoxyquazepam, hydroxy-oxoquazepam, and hydroxy-methoxy-oxoquazepam, which have the hydroxy and methoxy groups on the fluorophenyl group, and dihydroxy-oxoquazepam and dihydroxy-methoxy-oxoquazepam, which have one hydroxy group at the 3-position of the seven-membered ring and the other hydroxy group and the methoxy group on the fluorophenyl group. We demonstrated that LC-IT-TOF MS was a useful tool for determining the structure of the metabolites. However, the exact locations of the hydroxy and methoxy groups on the fluorophenyl group could not be identified.
authors: Department of Legal Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. Electronic address: yamakoji@nms.ac.jp.
authors: Koji
authors: K
authors: Yamaguchi
authors: Shimadzu Corporation Global Application Development Center, Hadano, Kanagawa, Japan.
authors: Takahiro
authors: T
authors: Goda
authors: Shimadzu Corporation Global Application Development Center, Hadano, Kanagawa, Japan.
authors: Satoshi
authors: S
authors: Yamaki
authors: Department of Legal Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Youkichi
authors: Y
authors: Ohno
mesh_terms: D001569:Benzodiazepines / Q000032:analysis / Q000737:chemistry*; D001570:Benzodiazepinones / Q000737:chemistry; D001646:Bile / Q000737:chemistry; D053593:Forensic Toxicology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000032:analysis / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D015394:Molecular Structure
chemical_list: C584129:3-hydroxy-2-oxoquazepam; D001570:Benzodiazepinones; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C025130:quazepam
keywords: Ion trap; Liquid chromatography; Metabolite; Quazepam; Time-of-flight mass spectrometry