Determination of metapramine, imipramine, trimipramine and their major metabolites in plasma by reversed-phase column liquid chromatography.

The determination of metapramine, imipramine, trimipramine and their desmethyl metabolites after alkaline diethyl ether extraction from plasma is achieved by column liquid chromatography using two internal standards and mu Bondapak C18 column. Elution is carried out isocratically at 1 or 0.6 ml min-1 with two mixtures of acetonitrile-potassium dihydrogen phosphate-distilled water (45:55:10 for metapramine and its metabolites; 45:50:5 for imipramine, trimipramine and their metabolites). Detection is monitored by absorption at 254 nm. The detection limit is less than 5 ng ml-1 for each compound. The coefficients of variation (within-day and day-to-day) for the eight compounds are less than 11.3%. Interference from several possible co-medications is discussed. The technique can be used for routine therapeutic monitoring of the antidepressants as well as analytical toxicology. However, the three antidepressants cannot be analysed simultaneously by this method because metapramine requires a different elution system and imipramine interferes with monodesmethyltrimipramine (retention times 8.90 and 8.60 min, respectively).