Tricyclic Antidepressant Determination in Human Plasma by Gas-Liquid Chromatography Using Nitrogen-Phosphorous Detection: Application to Single-Dose Pharmacokinetic Studies

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Abstract
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.