Determination of dosulepin and its metabolite: application of high-performance liquid chromatography with electrochemical detection.
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.
D000818:Animals; D001711:Biotransformation; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D003988:Dibenzothiepins / Q000032:analysis*; D004308:Dothiepin / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D004563:Electrochemistry; D007202:Indicators and Reagents; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D003988:Dibenzothiepins; D007202:Indicators and Reagents; C030224:northiaden; D004308:Dothiepin