DETERMINATION OF IMIPRAMINE AND 7 OF ITS METABOLITES IN HUMAN LIVER-MICROSOMES BY A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD

The metabolism of the widely used antidepressant drug imipramine is subject to marked interindividual variation. A sensitive and specific reversed-phase high-performance liquid chromatography method for the simultaneous determination of imipramine and seven of its metabolites in human liver microsomal preparations was developed. These metabolites include 10-hydroxydesipramine, 10-hydroxyimipramine, 2-hydroxydesipramine, 2-hydroxyimipramine, desipramine, didesmethylimipramine, and imipramine N-oxide. The detection limit for imipramine and the metabolites was approximately 20 pmol. At concentrations of 100 and 500 pmol per tube, the reproducibility showed a co-efficient of variation <10%, except for the 2-hydroxydesipramine (16%), 2-hydroxyimipramine (15%), and imipramine N-oxide (17%), all three at 100 pmol per tube. Linear standard curves were obtained for all the compounds within a concentration range of 50 to 1000 pmol per tube. This assay will provide a tool to assess the contribution of different enzymes to the formation of imipramine metabolites. © 1990.