Degradation of citalopram by simulated sunlight

Abstract

Citalopram (CIT), 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-5-phthalancarbonitrile, a selective serotonin reuptake inhibitor, is one of the most widely used antidepressants for the treatment of anxiety, obsessional, and control disorders. The degradation of the pharmaceutical CIT hydrogen bromide in water was investigated in the dark and in a growth chamber outfitted with fluorescent lamps simulating the ultraviolet output of sunlight at 25 degrees C. No significant degradation could be detected in dark controls in any aqueous solution investigated over a period of 30 d. Citalopram degraded less than 0.5% at pH 5 and pH 7 during the 30-d exposure period under simulated sunlight. However, at pH 9, CIT moderately degraded, with a half-life of 65 d via a pseudo-first order kinetic model. Degradation was faster in synthetic humic water (half-life, 24 d) and in natural waters (half-lives, 14 and 43 d) than in pH 9 buffer, indicating photosensitization by humic acid or other materials in water. Two photoproducts were detected over the irradiation period, and their structures were identified as N-desmethylcitalopram (DCIT) produced by N-demethylation as a major product and CIT N-oxide by N-oxygenation as a minor product by liquid chromatography-electrospray ionization-mass spectrometry. The DCIT appeared to be hydrolytically and photolytically stable in aqueous environments. In conclusion, CIT and DCIT were relatively stable in various solutions including natural waters. However, they may dissipate from the aqueous phase to some extent, possibly because of adsorption in real environments where soils and sediments exist.