Electrochemical Oxidation of Catechol in the Presence of Methimazole: Application of Square-Wave Voltammetric Detection of Methimazole to Pharmaceutical Formulations

The electrochemical oxidation of catechol has been studied in 0.1 M phosphate (pH 7.0) buffered aqueous solutions in the presence of methimazole as a nucleophile. Cyclic voltammetric and controlled-potential coulometric data demonstrate the occurrence of nucleophilic addition to the electrochemically-generated benzoquinone molecule following a 1-4 addition mechanism. The resulting ring-substituted product is more easily oxidized than the original catechol, leading to an increase in the anodic current, which is proportional to the concentration of methimazole. The second-order rate
constant for the homogeneous reaction between the electrochemically-generated o-quinone and methimazole was estimated by comparison of digital simulations of the cyclic voltammograms and experimental data. Square-wave voltammetry was applied to provide a very sensitive voltammetric determination of methimazole with a linear peak current response over the concentration range of 0.03 to 40μM, with a detection limit of 12nM. The presence of excipients commonly found in pharmaceutical preparations produced no appreciable change to the voltammetric response of Methimazole.