Voltammetric determination of nitroimidazopyran drug candidate for the treatment of tuberculosis

Abstract

PA-824 (2-nitro-6-(4-trifluoromethoxy-benzyloxy)-6,7-dihydro-5H-imidazo [2,1-b][1,3]oxazine) a nitroimidazopyran drug candidate for the treatment of tuberculosis was electrochemically studied with the aims of to propose a new electroanalytical method and to investigate the potential of an electrochemical system to mimic phase I reduction metabolism in PA-824. The electrochemical behavior was studied using tast polarography, differential pulse polarography. differential pulse voltammetry and cyclic voltammetry. PA-824 was electrochemically reducible showing one reduction peak due to the four-electron reduction of the nitro group to form the hydroxylamine derivative. A method for the determination of PA-824 by differential pulse polarography and differential pulse voltammetry at pH 7 were proposed. The differential pulse polarography method has adequate accuracy and precise with a mean recovery of 101.11% and a standard relative deviation of 2.27%. The detection limit was 2.23 x 10(-7) M. Furthermore. for comparative purposes an alternative differential pulse voltammetry and UV spectrophotometric methods were developed. On the other hand. from the electrochemical point of view, PA-824 shows similar reduction capabilities that metronidazole supporting the hypothesis that both drugs could share a similar reductive metabolism.