Determination of imipramine and seven of its metabolites in human liver microsomes by a high-performance liquid chromatographic method

✍ Scribed by Tanja B. Zeugin; Kim Brosen; Urs A. Meyer

• Publisher: Elsevier Science
• Year: 1990
• Tongue: English
• Weight: 396 KB
• Volume: 189
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1016/0003-2697(90)90052-b

✦ Synopsis

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-hydroxy-desipramine, 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 coefficient of variation less than 10%, except for the 2-hydroxy-desipramine (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.