Oxidation and Reduction of Hydrazones-Risk Factors Related to the Manufacture and Stability of the Drugs.

This study aimed to evaluate the use of electrochemistry to generate the oxidation and reduction products of active pharmaceutical ingredients (APIs) with a hydrazone group, including dantrolene, nitrofurantoin, furazidine, and nitrofural. In the first step, cyclic voltammetry was employed to assess the electroactivity of these compounds. In the second step, the transformation products of selected APIs following electrochemical oxidation and reduction were analyzed using the ROXY EC System equipped with a µ-PrepCell™ 2.0, coupled with a high-resolution Q-TOF mass spectrometer. The identification of transformation products was based on accurate mass, isotopic distribution, and fragmentation pattern. Seventeen API impurities were identified in this study, contributing to insights into drug stability and potential risks associated with their manufacture. Experimental findings were supported by the quantum mechanical DFT calculations of the molecular energies. In addition, using commercially available in silico software, the predicted metabolic products were compared with those obtained by experimental methods. The electrochemical approach proved useful as a test for determining the stability of compounds, the detection of new impurities and structure determination using high-resolution mass spectrometry.