High performance liquid chromatographic determination of dothiepin and northiaden in human plasma and serum

A method has been developed for the separation and measurement of dothiepin and the N-demethyl metabolites, 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 with +/-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.