The most important pathways in phase I metabolism are enzyme-catalyzed oxidations. Therefore, various oxidation methods, such as metalloporphyrins, Fenton reaction, electrochemical reactions and titanium dioxide (TiO₂) photocatalysis, have been studied as alternatives for in vitro phase I metabolism studies.^1-3   The aim of this study was to further investigate the feasibility of TiO₂ photocatalysis for imitation of phase I metabolism of anabolic steroids.

The photocatalytic reactions of testosterone, methyltestosterone, metandienone, nandrolone and stanozolol were carried out in liquid phase using TiO₂ Degussa P25 particles and ultra violet light. The metabolism reactions were studied in vitro using human liver microsomes (HLM). The samples were analyzed with ultra high performance liquid chromatography electrospray quadrupole time-of-flight mass spectrometry in positive ion mode.

For all the steroids studied, the main reactions observed both in TiO₂ photocatalysis and HLM incubations were dehydrogenation, hydroxylation or combination of these two. Several isomers of hydroxylation and hydroxylation+dehydrogenation products were formed in both systems. Based on the same mass, retention time and similarity of the product ion spectra, many of the products observed in HLM reactions were also formed in TiO₂ photocatalytic reactions. However, products characteristic to either of the systems were also formed.

In conclusion, TiO₂ photocatalysis is a rapid and simple method for imitation of phase I metabolism reactions. The main reactions were same in TiO₂ photocatalysis and HLM reactions. However, the stereochemistry of the products might be different and the feasibility of photocatalytic reactions for simulation of drug metabolism needs to be further studied.