| Popis: |
Tricyclic antidepressants are extensively metabolised by microsomal oxidation enzymes of the liver [1-4], so that following oral administration the level of unchanged drug in plasma or urine is low [5-8]. The metabolism of dothiepin hydrochloride (DP) was investigated by Crampton et al. [9] and the structures of four of its metabolites are shown in Fig. 1. Northiaden (monodesmethyldothiepin, NOR), dothiepin suiphoxide (DP-SO) and northiaden sulphoxide (NOR-SO) were identified in rat, cat, dog and human urine, and the glucuronide of hydroxydothiepin in rat urine after oral administration of (laC)labelled-DP. Rees reported that the excretion of DP and NOR was small and that sulphoxidation was the main metabolic pathway of DP in man after an oral dose of 14CDP [10]. The authors have recently identified two new metabolites, dothiepin sulphone (DP-SO2) and northiaden sulphone (NOR-SO2) in rat urine using gas chromatography-mass spectrometry [11]. This report describes a reversed-phase high-performance liquid chromatographic (HPLC) method of analysis for DP-SO, DP-SO2, NOR-SO and NOR-SO2 in human urine following a single oral dose (25 mg) of dothiepin. |
