Metabolite patterns of the carbonic anhydrase inhibitors Brinzolamide and Dorzolamide: potential markers for the route of application

Code: 23C05MT

The two carbonic anhydrase inhibitors brinzolamide (BA) and dorzolamide (DA) are prohibited in sports after systemic administration (ophthalmic permitted) only, thus, the analytical evidence for the administration route represents a desirable tool in doping controls. The diuretic effects of BA and DA are responsible for the classification as masking agent, which are prohibited at all times (in- and out-of-competition). Preliminary results showed that the metabolism of BA and DA differs for the different application routes. Additionally, it is well known that these substances (together with their metabolites) are enriched in the red blood cells, with a resulting half-life of several weeks after administration. In the present study the in-vivo metabolism of BA and DA after ophthalmic (eye drop) and systemic (oral) administration to pigs will be evaluated with special focus on the characteristic application route derived metabolism. The metabolite pattern of BA and DA will be evaluated and compared to samples obtained from patients that therapeutically apply either BA or DA as ophthalmic preparations. The analysis of the parent drug as well as their metabolites are planned by means of liquid chromatography coupled to high resolution mass spectrometry.