Switch from The Traditional RPLC Method to the Green RPLC Methods in The Determination of The Ionization Constant (pK _a ) of Favipiravir

Abstract In this study, the ionization constant (pK a ) of favipiravir was determined using both green and the traditional RPLC methods. To determine these values, acetonitrile‐water and methanol‐water mixtures were used in the traditional RPLC methods, while ethanol‐water and micellar solvent‐free mixtures were used in the green RPLC methods. The pK a value of favipiravir was calculated by evaluating the chromatographic data obtained in the investigated hydro‐organic and micellar solvent‐free mixtures using two different calculation methods. In the determination of their pK a values in water from the pK a values of the investigated compounds determined in hydro‐organic mixtures, the relationship between some macroscopic values of acetonitrile, methanol, ethanol and the values was used, while the values of the compounds could be determined directly in micellar solvent‐free mobile phases. It was found that the directly and indirectly calculated values were quite compatible with each other. Using the value calculated for favipiravir, the ionization percentages at different pH values (1–12) were calculated by the Henderson‐Hasselbalch equation. The environmental impact of the RPLC methods used in this study was assessed using the Green Metrics tools GAPI and AGREE.