Electrochemical and spectroelectrochemical behavior of the main photodegradation product of nifedipine: the nitrosopyridine derivative.

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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Núñez-Vergara LJ,Bollo S,Fuentealba J,Sturm JC,Squella JA

doi

10.1023/a:1015112216360

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

522-9

issue

4

eissn

0724-8741

issn

1573-904X

journal_volume

19

pub_type

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