Enantioselective determination of pazinaclone, a new isoindoline anxiolytic, and its active metabolite in rat plasma by high-performance liquid chromatography.
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.
Kondo
T
T
Drug Analysis and Pharmacokinetics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Hamasaki
K
K
Yamaguchi
M
M
Aoki
I
I
Yoshida
K
K
Yoshimura
Y
Y
Tanayama
S
S
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
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D009287:Naphthyridines; D013141:Spiro Compounds; C060382:pazinaclone