Increased phototoxicity of hydrochlorothiazide by photodegradation

The photodegradation products of hydrochlorothiazide produced by ultraviole t (UV) radiation were investigated for their phototoxicity utilizing the ph otohemolysis and Candida albicans tests. Hydrochlorothiazide was irradiated for 30, 60, 90 and 120 min with a 250 W xenon are lamp using a WG295 cut-o ff filter. Irradiation of hydrochlorothiazide resulted in the gradual decre ase of all three absorption bands (225, 270 and 320 nm), the blue shift of the 225 nm band, and the appearance of a new band around 290 nm, Since prev ious results demonstrated that photosubstitution of chloride could occur, t he main product of this photolysis most likely is ethoxyhydrochlorothiazide , The photohemolysis test revealed a significant increase in photohemolysis observed in the photodegradation products produced after 60, 90 and 120 mi n of UV irradiation. This increase in hemolysis value directly correlated w ith the UV-irradiation time. However, there was no significant phototoxic k illing of yeast in the Candida albicans test. This suggests photodegradatio n products of hydrochlorothiazide may play an important role in phototoxici ty by acting on the cell membrane, but not on DNA, Considering the high in vitro phototoxicity observed in bendroflumethiazide and the data presented here, substitution of chloride seems to be responsible for the increased ph ototoxicity of hydrochlorothiazide.