Ion-pair liquid chromatography of steady-state plasma levels of chlorimipramine and demethylchlorimipramine.

A method for the determination of chlorimipramine and its metabolite demethylchlorimipramine in the plasma of depressed patients during treatment is described. The method involves extraction of the parent drug, its metabolite and the internal standard from plasma, back-extraction into an acidic aqueous phase and re-extraction into a small volume of organic phase. Separation and quantitation are carried out by ion-pair partition chromatography with UV detection. Accurate determination if possible down to levels of 30 and 60 nmole per liter of plasma for chlorimipramine and the metabolite, respectively, when 1 ml of plasma is used. The coefficient of variation is 7.3% or less at different levels for chlorimipramine and demethylchlorimipramine. Plasma levels of the parent drug and the metabolite measured by this liquid chromatographic method and by a gas chromatographic procedure with electron-capture detection were in good agreement (r = 0.98). The steady-state plasma level of the metabolite was always higher than that of the parent drug in the 34 depressed patients investigated. The mean ratio between the metabolite and the parent drug was 2.7 +/- 1.1 (S.D.) Large inter-individual differences in the levels of the two compounds in patients receiving similar doses were found.