Favipiravir (FAV) is a prodrug with a proven antiviral efficacy against coronavirus 2. Close therapeutic monitoring of FAV is crucial for COVID-19 patients due to its variable dosing, complex pharmacokinetics, and notable drug interactions. This study presents a novel, selective electrochemical sensor for FAV detection, using a carbon paste electrode (CPE) modified with multi-walled carbon nanotubes (MWCNTs) and calcium-doped ZnO nanoparticles (Ca-ZnO NPs). Characterization of the Ca-ZnO NPs was performed using Fourier-transform infrared spectroscopy (FT-IR), field emission-scanning electron microscope (FE-SEM), and X-ray photoelectron spectroscopy (XPS). Several operational parameters were optimized, including carbon paste composition, buffer selection, pH, and electrochemical waveform settings. Under optimized conditions, an oxidation signal of FAV was identified at approximately + 1.22 V versus an Ag/AgCl reference electrode in Britton-Robinson buffer (BRB) at pH 4.0. Differential pulse voltammetry (DPV) facilitated the detection of FAV across a wide dynamic concentration range of 0.6–100.0 µM, with detection and quantification limits of 0.17 and 0.51 µM, respectively. The developed method demonstrated high selectivity towards FAV, effectively distinguishing it from its acidic degradation product (ADP), qualifying it as a stability-indicating assay. Evaluations using the GAPI, AGREE, and RGB 12 metrics confirmed alignment with green and white analytical chemistry principles. Furthermore, this method was successfully applied to quantify FAV in human plasma, making it suitable for therapeutic drug monitoring (TDM) in COVID-19 patients.
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