Abstract
AD-5423, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[ 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 C 18 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 determinations 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.
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