Investigation of the photostability properties of memoquin, a quinone derivative for the treatment of Alzheimer's disease

Abstract

The photostability properties of memoquin, a multifunctional compound in preclinical development for the treatment of Alzheimer's disease (AD) were investigated in solutions exposed to radiations, using a xenon arc lamp to simulate the natural sunlight. Reversed phase liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (LC–UV/DAD–ESI-MS/MS) was applied to follow the photodegradation and disappearance of memoquin after irradiation. Under optimized chromatographic conditions, memoquin was separated with high resolution from the photoproducts formed in the photoexposed solutions. The results showed that memoquin is more stable at physiological and acid pHs, while it has a slow degradation pattern at more drastic conditions such as basic pH ( t 1/2 = 389 min) and in methanolic solutions ( t 1/2 = 465 min). In the irradiated solutions the appearance of photoproducts with lower retention times and molecular weight than memoquin was observed, thus indicating that some fragments were lost from its structure. The photodegradation products were characterized by LC–ESI-MS/MS and LC–UV/DAD analysis. The photoreactive centers were found on the amino groups of the side chains while the 1,4-benzoquinone functionality was maintained. Conversely, memoquin was found to be stable in the dark. These results suggest that, with appropriate handling and storage, memoquin's activity is not impaired.