Green micellar solvent-free HPLC and spectrofluorimetric determination of favipiravir as one of COVID-19 antiviral regimens.

Quality control (QC) of pharmaceutical products requires fast, sensitive as well as economic methodologies in order to provide high through output at low cost which are the main aspects considered by such economic facilities. Meanwhile, the ecological impacts must be considered by researchers to minimize the hazardous effects of research laboratories. Favipiravir (FAV) is an antiviral agent recently approved for treatment of COVID-19 infections during 2020 pandemic crisis, so the size of its production by international pharmaceutical corporations evolved dramatically within the past few months. Two novel simple, sensitive, and green methods were developed and validated for FAV determination based on solvent-free micellar LC and spectrofluorimetry techniques. To improve FAV native fluorescence, several factors were studied including solvent type, buffering, pH and added surfactants. The best sensitivity for FAV fluorescence was obtained in Britton-Robinson buffer (pH 4) at 436 nm after excitation at 323 nm within concentration range of 20-350 ng mL. Another HPLC method was validated using C18-RP (5 µm, 250 × 4.6 mm) stationary phase and solvent-free mobile phase consisting of (0.02 M Brij-35, 0.15 M SDS, and 0.02 M disodium hydrogen phosphate, pH 5.0) isocratically eluted at a flow rate of 1 mL min and detection wavelength of 323 nm. LC method was validated across concentration range of 10-100 µg mL and FAV eluted in 3.8 min. The methods were validated according to the FDA guidelines and were applied successfully for determination of FAV in its marketed tablet dosage forms and in spiked human plasma samples. The proposed methods are eco-friendly since they are typically based on biodegradable reagents in aqueous solvent-free phases, which was proven by their assessment on two recent greenness metrics (GAPI and AGREE) to prove their eco-friendly properties.