Temozolomide chemical degradation to 5-aminoimidazole-4-carboxamide – Electrochemical study

Abstract

The evaluation of the chemical degradation of temozolomide (TMZ), a potential anti-cancer drug, to its major metabolite 5-aminoimidazole-4-carboxamide (AIC), in aqueous solution with different pH values, was investigated at a glassy carbon electrode using cyclic and differential pulse voltammetry, and UV–Vis spectrophotometry. TMZ was incubated in aqueous solution, for different periods of time, and the changes in TMZ electrochemistry behaviour detected. The TMZ reduction is a pH-dependent irreversible process on the tetrazinone ring causing its irreversible breakdown. TMZ oxidation is a pH-dependent irreversible process that occurs in two consecutive charge transfer reactions. TMZ chemical degradation was electrochemically detected by the increase of the TMZ anodic peak current and the disappearance of the TMZ cathodic peak. The rate of chemical degradation increases with increasing pH and the mechanism corresponds to TMZ chemical degradation to AIC. The electrochemical behaviour of AIC over a wide pH range, was also investigated using cyclic, differential pulse and square wave voltammetry, AIC oxidation is an irreversible, diffusion-controlled process, pH-dependent up to a pH close to the pKa, and occurs in two consecutive charge transfer reactions, with the formation of two reversible redox products. A mechanism for AIC oxidation is proposed.