Electrochemical Oxidative Degradation and Trapping of the Mefenamic Acid Drug as a Redox-Active Hydroxy Metabolite on a Carbon Black Surface: Mediated Oxidation and Sensing of Thiol Biomarker

The elucidation of potential molecular structures and metabolites of pharmaceutical drugs remains a key area of research in medicinal chemistry, particularly due to drug-induced toxicity reactions. In this study, the electrochemical degradation of mefenamic acid (MFA) was conducted, leveraging biomimetic electron-transfer mechanisms. A carbon black (CB)–modified glassy carbon electrode (GCE) was employed as a biomimetic system to facilitate the in situ electrochemical conversion of MFA-drug into redox-active hydroxylated MFA metabolite (MFA-Redox). The chemically modified electrode (CME) demonstrated a surface-confined electronic feature of MFA-Redox, with a surface excess of 14.1 × 10⁻⁹ mol cm⁻² under physiological conditions. Various physicochemical and chemical characterization techniques, including liquid chromatography-mass spectrometry (LC–MS/MS) analysis, confirmed the hydroxylated metabolite of MFA (M_w = 305.05 g/mol). Furthermore, the CME was used for the mediated oxidation of thiol groups, using cysteine (CySH)—a biomarker for cellular redox balance in physiologically neutral pH—as a model compound. This resulted in a well-defined, diffusion-controlled oxidation peak current. The Michaelis–Menten (MM) enzymatic kinetics model was applied to describe the oxidation process, yielding key kinetic parameters: the MM rate constant (K_M) of 0.060 mM, the first-order catalytic rate constant (k_c) of 0.4 s⁻¹, and the heterogeneous electron-transfer rate constant (k'_ME) of 9.7 × 10⁻² cm s⁻¹. In a separate electroanalytical study, the performance of the CME for CySH detection was evaluated using amperometric i-t curves. The CME demonstrated a linear concentration range from 100 µM to 1 mM, with a sensitivity of 1.045 nA/µM and a detection limit of 3 µM. Importantly, the CME showed excellent selectivity, with no interference from uric acid, ascorbic acid, dopamine, glucose, and creatinine.