Stereoselective determination of a new antidepressant, E2011, and its diastereoisomer as a metabolite by high-performance liquid chromatography.
A stereoselective HPLC method has been developed for the determination of E2011 (compound I) and one of its metabolites and diastereoisomers, ER-20593 (compound II), in plasma. The two substances and the internal standard were extracted from plasma, followed by two purification steps. In the first step, a minicolumn, Bond Elut C18, was used and in the second step, another minicolumn, Bond Elut Si, was used for purification of the compounds. After the purification, the compounds were analyzed by HPLC with two Chiralpak AD columns. In this procedure, compounds I and II were stable and there was no chiral inversion. The within-day and the between-day assays were performed in rat plasma, where compounds I and II existed simultaneously. The within-day and the between-day precisions of compound I were 2.0 approximately 10.1% and 1.3 approximately 7.1%, and the within-day and the between-day accuracies were -8.2 approximately +3.0% and -6.6 approximately +4.0% in the concentration range 0.003-10 microg ml(-1). The within-day and the between-day precisions of compound II were 1.7 approximately 16.9% and 0.9 approximately 4.5% and the within-day and the between-day accuracies were -9.0 approximately +2.4% and -5.6 approximately +3.8% in the concentration range of 0.005-0.5 microg ml(-1). QC samples for compound I and II were stable for at least 3 months. The method was applied to measure the levels of compound I and II in the rat plasma after oral administration of compound I.
Naitoh
T
T
Department of Pharmaceutical Regulatory Affairs, Eisai Co., Ltd., Bunkyo-ku, Tokyo, Japan.
Kakiki
M
M
Kawaguchi
S
S
Kagei
Y
Y
Horie
T
T
D000818:Animals; D000928:Antidepressive Agents / Q000097:blood*; D052160:Benzothiazoles; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000097:blood*; D010080:Oxazoles / Q000097:blood*; D023303:Oxazolidinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013844:Thiazoles / Q000097:blood*
D000928:Antidepressive Agents; D052160:Benzothiazoles; C091708:E 2011; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; D013844:Thiazoles