Determination of dosulepin and its metabolite: application of high-performance liquid chromatography with...

Dosulepin, 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenzo [b,e]thiepin hydrochloride, is a thio analogue of amitriptyline and is used for the treatment of anxiety and affective disorders. The present study developed a simple and sensitive procedure for the determination of this compound and its metabolite, northiaden, by a combination of high-performance liquid chromatography with electrochemical detection. Hydrodynamic voltammograms demonstrated an optimal applied potential at 1300 mV for both dosulepin and northiaden. A mobile phase consisting of 0.1 M acetate buffer-acetonitrile-perchloric acid-trichloroacetic acid (50:50:2:1.5) provided the best separation of the drugs. The extraction procedure, which used a heptane-isoamyl alcohol (99:1) mixture, was successfully applied with a recovery of over 90%. A preliminary pharmacokinetic study was performed by the proposed method.