title: Enantioselective determination of pazinaclone, a new isoindoline anxiolytic, and its active metabolite in rat plasma by high-performance liquid chromatography.
abstract: A sensitive and specific high-performance liquid chromatographic method has been developed for the simultaneous determination of the enantiomers of pazinaclone (DN-2327), a new anxiolytic agent, and those of its active metabolite, M-II, in rat plasma. Organic solvent extraction of pazinaclone, M-II, and internal standard (I.S.) in plasma was followed by separation of the analytes from other metabolites using an achiral reversed-phase column. Fluorescence detection was employed with excitation and emission wavelengths of 328 and 367 nm, respectively. Separation of all the enantiomers and I.S. was then accomplished with normal- and chiral-phase columns connected in series. For each analyte, the lower quantitation limit was 0.5 ng/ml. The assay has been applied to a chiral inversion study in rats. Chiral conversion from one enantiomer of pazinaclone to the other hardly occurred. This method is suitable for enantioselective pharmacokinetic and toxicokinetic studies in animals.
authors.affiliation: Drug Analysis and Pharmacokinetics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: K
authors.initials: K
authors.lastname: Hamasaki
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: I
authors.initials: I
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: S
authors.initials: S
authors.lastname: Tanayama
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D054833:Isoindoles; D008297:Male; D009287:Naphthyridines / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013141:Spiro Compounds / Q000097:blood*; D013237:Stereoisomerism
chemical_list: D014151:Anti-Anxiety Agents; D054833:Isoindoles; D009287:Naphthyridines; D013141:Spiro Compounds; C060382:pazinaclone