Antidepressants are commonly used for depression and anxiety. It is known that most drugs are metabolized by enzymes within the liver. The enzymes metabolize drugs by altering them to become more polar so that they can be excreted through the urine or bile. As a future pharmacist, I want to know how antidepressants are altered within the body before I distribute them. This study was done to determine the outcome of metabolism within three different antidepressants: venlafaxine (Effexor), duloxetine (Cymbalta) and escitalopram (Lexapro). 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 37C. Each sample was subjected to the compact mass spectrometer fitted with a C18 reverse phase column. The results indicated that all three drugs underwent N-demethylation but not aromatic hydroxylation during metabolism. When looking at the area of the peaks within each metabolized drug, duloxetine metabolized the most out of all three drugs. Up to 30-70% of duloxetine was metabolized. Several controls were also incubated and analyzed, such as the mixture without the drug, the mixture without NADPH-generating system, the mixture without the rat liver microsome and a mixture of just the drug and buffer. Some of the controls without the drug or the microsome still showed MS peaks with the same molecular weight as the drugs or the metabolites. These peaks could indicate that there are contaminants within the solvent or the phosphate buffer that have similar molecular weights. The future goal is to repeat these experiments using HPLC/CMS to further separate the metabolites. Using different drugs would also explain the outcome of metabolism a little further, such as if a drug can be both demethylated and hydroxylated.
Research Report, Poster, Final Report Form