Photostability studies of ketoconazole: isolation and structural elucidation of the main photodegradation products

The purpose of this study was to obtain information on the photochemical properties of ketoconazole, an antifungal agent. Photodegradation of ketoconazole in solution and shampoo under exposure to UV-C (254 nm) and UV-A (352 nm) radiations as well as daylight was monitored by HPLC. Separation of ketoconazole from its degradation products was obtained with monoisopropylamine - methanol (2:500 v/v) and amonium acetate- water (1:200 w/v) (7:3 v/v) as mobile phase on a LiChrospher® 100 column RP-8, 5 μm (150 mm x 4.6 mm) and a flow rate of 1 ml/min. The main protodegradation products: (cis-1-acetyl-4-{4-[[2-(2-chlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3- dioxolan-4-yl]methoxy]phenyl}piperazine and (cis-1-acetyl-4-{4-[[2-(4-chlorophenyl)-2-(1H-imidazol- 1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl} piperazine, were isolated and characterized by HPLC-MS and NMR spectrometry. The results indicated photodechlorination of ketoconazole when exposed to light and a significant decrease in antifungal activity. Colegio de Farmacéuticos de la Provincia de Buenos Aires