Tricyclic antidepressant determination in human plasma by gas-liquid chromatography using nitrogen-phosphorous detection: Application to single-dose pharmacokinetic studies

A method with adequate sensitivity (to 0.50-0.75 ng/ml) for single-dose pharmacokinetic studies which utilizes gas-liquid chromatography with nitrogen-phosphorous detection for tricyclic antidepressants (imipramine, desipramine, amitriptyline, nortriptyline, and doxepin) is described. A basic (pH 13) extraction with acid back-wash and subsequent basic reextraction is used for plasma sample preparation. Standard curves, using clomipramine as the internal standard, are linear for concentrations from 1 to 200 ng/ml for all tricyclic antidepressants. Applicability of the method is demonstrated by a pharmacokinetic study in a normal volunteer who received 12.5 mg imipramine hydrochloride i.v.