Studies on the photostability and in vitro phototoxicity of Labetalol

The purpose of this study was to obtain information on the photochemical an d phototoxic properties of Labetalol, a beta-blocker drug. Preliminary info rmation on the drug photoreactivity was achieved using a flow system with a photochemical reactor on-line with a diode array detection system. Photoph ysical and photochemical investigations on the drug were performed in aqueo us solutions at different pH values using spectrophotometric and fluorimetr ic methods; the photodegradation quantum yield was found to be 2.7x10(-3) a t pH 5.8 and 1.5x10(-2) at pH 11.5. Forced photodegradation of labetalol so lutions under exposure to UVA-UVB radiations (xenon are lamp) was monitored by reversed-phase liquid chromatography. The main photodegradation product s were isolated and characterized by NMR and mass spectrometry; labetalol w as found to give 3-amino-1-phenylbutane and salicylamide-4-carboxaldehyde a s the main photoproducts. Preliminary phototoxic testings on human keratino cyte cultures were performed evaluating the viability of the cells by the n eutral-red uptake assay; mutagenic and photomutagenicity tests were also ca rried out based on Salmonella typhimurium strains. As a result, labetalol w as found to be photolabile, mainly in alkaline medium, but evidences of sig nificant phototoxic and photomutagenic effects by the drug were not observe d. (C) 2001 Elsevier Science B.V. All rights reserved.