AbstractFor the treatment of Parkinson's disease, as one of the most frequent diseases of the central nervous system, several key enzymes for dopamine metabolism [e. g. catechol‐O‐methyl transferase (COMT)] are drug targets. For an efficient and long‐lasting treatment, the activity of this enzyme should be monitored. In this study, an electrochemical approach using differential pulse voltammetry (DPV) is introduced for the activity determination. The applied electrode material, fluorine‐doped tin oxide (FTO), is characterized by a clear discrimination between substrate and product of COMT, a high stability of the dopamine signal during consecutive measurements, and a linear dependency on the dopamine concentration in the range of the maximum reaction rate of COMT. Despite these advantageous results, dopamine detection in the complete activity assay is influenced by each of the added essential assay components, even though none of the added components reveal a current signal at the FTO electrode itself. After adjusting the potential range and the assay composition, these effects can be circumvented. By following the dopamine concentrations during COMT action, it can be shown that the activity of COMT can be detected by using differential pulse voltammetry (DPV) at an FTO electrode and, by analyzing different COMT amounts, quantification can be demonstrated.