IN-VITRO PHOTODEGRADATION OF CHLORPROMAZINE

The in vitro photodecomposition of chlorpromazine (CPZ) was investigat ed with the aim to evaluate possible reactive determinants that could play a role in the occurrence of the in vivo-observed photosensitivity . In view of the in vivo situation, CPZ was dissolved in low concentra tion in buffered aqueous solution (pH 7.4) or in dilute human serum an d irradiated with low intensity (5-7 W m(-2)) UV-A and UV-B. No distin ct difference was found between UV-A or UV-B irradiation as far as pho toproduct formation is concerned. This suggests the same degradation m echanism at both wavelength ranges. In buffered aqueous solution, irra diation of CPZ resulted in 65 and 90% 2-hydroxypromazine (PZOH), 5 and 7% promazine (PZH) and 2 and 0% chlorpromazinesulfoxide (CPZSO) under aerobic and anaerobic conditions, respectively. In dilute human serum , there was only a shift in the PZH/PZOH ratio, probably as a result o f H-atom or electron donation by sulfur containing groups present in p roteins. The results demonstrate that photodegradation of CPZ in vitro , under conditions relevant to the in vivo situation, proceeds almost entirely by dechlorination rather than by radical cation formation (th e essential pathway of CPZSO production). Thus we conclude that the th iyl radical cation probably does not play a major role in the in vivo- observed phototoxic reactions.