A method has been developed for the separation and measurement of dothiepin and the N-desmethyl metabolite, northiaden, in human plasma or serum by high performance liquid chromatography. The method uses a structurally-related drug, amitriptyline, as an internal standard and provides a limit of detection of about 10 ng/ml for each component. At a concentration of 20 ng/ml, northiaden and dothiepin could be measured within ±11% and ± 6% of the mean respectively and at 200 ng/ml within ± 3% and ± 1% of the mean. The method has been applied to the analysis of serum from patients undergoing dothiepin therapy.
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