Determination of ionization/protonation constant values of some guanine derivative drugs by traditional/ green RPLC and UV–Vis spectrophotometric methods.

[Display omitted] • The pK a values were alternatively determined using the eco-friendly green RPLC methods. • The agreement between theoretical and experimental data is given by the LSER approach. • The ionization behavior of the compounds was determined by RPLC methods. • Aqueous p K a values were calculated for hydro-organic and micellar solvent-free mixtures. In this study, the green reverse-phase liquid chromatography (RPLC) method was used in addition to the traditional RPLC method to determine the ionization/protonation constants (pK a) of the guanine derivatives ganciclovir, valacyclovir, and valganciclovir. The determination of these values was carried out in binary acetonitrile–water mixtures (for the traditional RPLC method), ethanol–water binary mixtures (for the green RPLC method), and in aqueous solution of a micelle-forming surfactant (for pure micellar chromatography). The pK a values s s p K a of the compounds were calculated using the linear solvation energy relationship (LSER) method in the studied hydro-organic and micellar solvent-free mixtures. Moreover, the UV–Vis spectrophotometric method was used to compare the s s p K a values of ganciclovir, valaciclovir, and valganciclovir obtained in a acetonitrile–water medium using another method. The pK a values ​​of the examined compounds in water were calculated using the linear relationship between the s s p K a values ​​determined in hydroorganic mixtures and some macroscopic values ​​of acetonitrile and ethanol. Additionally, w w p K a values ​​were determined in the micellar solvent-free mobile phase. Subsequently, the w w p K a values calculated by these direct and indirect methods were compared and the agreement between them was excellent. By using the w w p K a value calculated for each compound, the ionization percentages were calculated at different pH (1–12) values with 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. The result of the investigation was that the environmental suitability of the green methods is satisfactory. [ABSTRACT FROM AUTHOR]