Detection of doxepin and its major metabolite desmethyldoxepin in hair following drug therapy

Doxepin is a tricyclic antidepressant that is widely prescribed for the treatment of mild depression. In this study, hair samples collected from a patient receiving 25 mg of doxepin daily were analyzed. Doxepin was administered to the patient for 4 months (June 15 to October 15, 1996). Five hair samples were collected: 1 and 3 months after doxepin therapy began and 1, 3, and 5 months after drug therapy ended. Solid-phase extraction was employed to isolate doxepin and its major metabolite desmethyldoxepin from the hair matrix, and gas chromatography-mass spectrometry (GC-MS) was used for quantitation of both drugs. Six-point standard curves (0.25-20 ng/mg) were prepared for both compounds with an internal standard (doxepin-d3). The standard curves for doxepin and desmethyldoxepin were linear over the range reported and had correlation coefficients of 0.984 and 0.985, respectively. The limit of quantitation for both analytes was 0.25 ng/mg of hair. In addition, the replicate analysis of control hair preparations was performed at two levels (2 ng/mg and 15 ng/mg) to determine intra- and interday variability. Doxepin and desmethyldoxepin were not detected in the patient's sample collected 1 month after doxepin therapy began. The samples collected 3 months after doxepin therapy began and 5 months after drug therapy was terminated had detectable amounts of doxepin and desmethyldoxepin. The highest concentrations of doxepin (mean, 0.59 ng/mg) and desmethyldoxepin (mean, 0.40 ng/mg) were found 5 months after doxepin therapy began, which was also 1 month after the patient had stopped using the drug. Five months after doxepin therapy was terminated, the drug and its metabolite were still present in the patient's hair. The concentration of doxepin in hair was always significantly higher than the concentration of desmethyldoxepin.