Reliable routine method for the determination of antidepressant drugs in plasma by high-performance liquid chromatography.

We describe a rapid and reliable method using high-performance liquid chromatography for the simultaneous measurement of plasma concentrations of currently prescribed antidepressants and their main metabolites (amitriptyline, nortriptyline, trans-10-hydroxy-nortriptyline, clomipramine, desmethylclomipramine, imipramine, desipramine, zimeldine, norzimeldine, doxepin, desmethyldoxepin, trimipramine and mianserin). The method involves a single extraction of plasma at pH 10.1 with hexane-acetonitrile (98:2), solvent transfer to and evaporation in a disposable glass tube and subsequent chromatography of the residue on a CN bonded-phase column using acetonitrile-methanol-phosphate buffer (pH 7.0) as mobile phase. Protriptyline is used as the internal standard. Calibration curves remain linear up to at least 200 micrograms/l, detection limits are 5 micrograms/l, absolute recoveries are over 92%, and precision (coefficient of variation) is 6.9%. Norzimeldine and 10-hydroxynortriptyline show lower recoveries, protriptyline and 10-hydroxynortriptyline higher detection limits. Adsorption to glassware and chemical decomposition during analysis are shown to be negligible. Psychoactive and other drugs frequently prescribed in combination with anti-depressants have been tested for their chromatographic properties under the same conditions.