Identification of Drug Metabolites of Antidepressant Medications, Clomipramine, Imipramine, and Nortriptyline in Rat Liver Microsome Using Compact Mass Spectrometry

Winona, Minnesota

Antidepressants are common prescription medications used to treat depression and anxiety. Most drugs are metabolized in the liver by enzymes that modify drugs to become more polar (i.e., through hydroxylation or demethylation). This modification allows for prescription medications to be excreted out of the body through urine or bile. As a future physician, I am interested in understanding how antidepressants are metabolized in the body. This study was done to determine the outcome of metabolism within three different antidepressants: Nortriptyline, Clomipramine, and Imipramine. These three drugs were mixed with rat liver microsomes and NADPH-generating system in phosphate buffer at pH 7.4. All samples were incubated for two hours at 37°C. Each sample was subjected to the compact mass spectrometer fitted with a C18 reverse-phase column. Neither of the three drugs showed a presence of metabolites. The future goal is to repeat these experiments using HPLC/CMS to separate the metabolites further. Using different drugs would also explain the outcome of metabolism a little further, such as if other drugs are both demethylated and hydroxylated.