Development of a green design reverse phase liquid chromatography method for determining the ionization profile of parabens.

The most popular method for determining chromatographic separation selectivity is an optimization method based on the use of different solvents. This article presents a sustainable chromatographic framework using reverse phase liquid chromatography (RPLC) to determine the ionization behavior of methylparaben, ethylparaben, propylparaben, and butylparaben, which are widely used in hydroorganic mixtures. In this study, retention-mobile phase pH data in methanol-water (40-55% v/v) and ethanol-water (30-45% v/v) mixtures were analyzed using a nonlinear regression (NLREG) approach to calculate the dissociation constant values of the compounds. Simultaneously, solvent strength selectivity was determined by varying the percentage of organic solvent in the mobile phase. Experimental studies were performed at 37 °C using a Gemini NX column (250 × 4.60 mm I.D., 3.5 µm). The solvatochromic solvent polarity parameter (E N T) was used to characterize the effect of ethanol and methanol concentrations in the mobile phase on the chromatographic behavior of the studied parabens. Determining the pK a values in the correct aqueous medium is necessary to predict the ionization-dependent solubility, chromatographic behavior, and biopharmaceutical performance of ionizable compounds. The values of parabens with intermediate solubility in aqueous medium were calculated using the mole fraction and dielectric constant values of the organic solvents used. The suitability of the developed methods to the twelve principles of green analytical chemistry (GAC) and the white analytical chemistry (WAC) approach was evaluated using established tools. This study is the first to report the qualitative determination of parabens within an environmentally friendly analytical framework, using potentially non-toxic solvents and energy, and reducing waste generation.