Abstract
Purpose. To characterize the electrochemical behavior of the photodegradation product of nifedipine, i.e., 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridine-carboxylic acid dimethyl ester (NPD) in different electrolytic media. We also evaluated the interaction between free radicals generated from NPD and xeno/endobiotics.
Methods. Tast polarography, differential pulse polarography, and cyclic voltammetry were used for the characterization. Controlled potential electrolysis and ultraviolet-visible spectroscopy were used to generate and to detect the nitroso radical anion.
Results. In protic media, the NPD derivative gave a reversible well-defined peak either on Hg or glassy carbon electrodes in a reaction involving two electrons and two protons to give the hydroxylamine derivative. In mixed aqueous-organic media (pH 9) and in aprotic media, nitroso radical anion was isolated and characterized, exhibiting second-order dimerization rate constant (k2) values of 11,300 ± 210 [Ms]−1 and 8,820 ± 78 [Ms]−1, respectively. Reactivity of the nitroso radical anion with relevant pharmacologic targets revealed a significant interaction with the tested endo/xenobiotics (cysteamine, GSH, N-acetylcysteine, and adenine).
Conclusions. Both in mixed and aprotic media, NPD generated free-radical species, the nitroso radical anion. Taking into account their respective interaction rate constants, the following tentative rank order of reactivity can be established as follows: cysteamine > N-acetylcysteine > GSH > adenine.
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Núñez-Vergara, L.J., Bollo, S., Fuentealba, J. et al. Electrochemical and Spectroelectrochemical Behavior of the Main Photodegradation Product of Nifedipine: The Nitrosopyridine Derivative. Pharm Res 19, 522–529 (2002). https://doi.org/10.1023/A:1015112216360
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DOI: https://doi.org/10.1023/A:1015112216360