Determination of a novel anti-psychotic agent AD-5423 and its metabolites in plasma by high-performance liquid chromatography with fluorescence detection.
AD-5423, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocy cloocta [b]pyridine, is a novel anti-psychotic agent. In order to investigate the pharmacokinetics of AD-5423, a simple and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of AD-5423 and its two N-oxidized metabolites (N-desethyl AD-5423 and AD-5423 N-oxide) in plasma. After pretreatment of a plasma sample by solid-phase extraction, AD-5423 and its metabolites were analyzed on a HPLC with fluorescence detection (335/410 nm). Chromatography was performed on two C18 reversed-phase columns connected by a switching system, with a mobile phase of acetonitrile-methanol-25 mM sodium phosphate buffer (pH 2.5) containing 25 mM sodium 1-heptanesulfonate (36:26:38 v/v/v). The method gives satisfactory accuracy and precision for the determination of AD-5423 and its metabolites. In human plasma, accurate determination are possible over the concentration ranges of 0.04-5 ng ml-1 for AD-5423 and 0.1-5 ng ml-1 for N-oxidized metabolites. The intra- and inter-day assay precision (R.S.D.) of AD-5423 (0.5 ng ml-1) were 3.6 and 7.2%, respectively. In plasma of experimental animals, the validated quantitative range are 0.1-100 ng ml-1 for both AD-5423 and its metabolites.
Matsuda
M
M
Department of Pharmacokinetics, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Sakashita
M
M
Yamaguchi
T
T
Fujii
T
T
D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D010879:Piperazines / Q000097:blood*; D010880:Piperidines / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence
D014150:Antipsychotic Agents; D010879:Piperazines; D010880:Piperidines; C079310:blonanserin