Identification of Drug Metabolites of Tricyclic Antidepressant Medications in Rat Liver Microsome Using Compact Mass Spectrometry

Kryzsko Commons Ballroom, Winona, Minnesota

Prescription antidepressants are commonly used drugs to treat depression and many other disorders. It is known that enzymes metabolize most prescription drugs within the liver by altering them to become more polar to allow for easy excretion through the urine or bile. This study was done to determine the outcome of metabolism of six different tricyclic antidepressants (TCA's): clomipramine, duloxetine, escitalopram, imipramine, nortriptyline, and venlafaxine. These six drugs were mixed with rat liver microsomes and an NADPH-generating system in a 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. Duloxetine, escitalopram, and venlafaxine all underwent N- demethylation but not aromatic hydroxylation during metabolism. On the other hand, clomipramine, imipramine, and nortriptyline failed to show N-demethylation nor aromatic hydroxylation. Several controls were incubated and analyzed, such as the mixture without the drug, the mixture without the NADPH-generating system, the mixture without the rat liver microsome, and a mixture of just the drug and buffer. The future goal is to repeat these experiments using HPLC/CMS to separate the metabolites further.