Green Analytical Chemistry-Oriented RPLC Method for Determining the Dissociation Constant of the Nootropic Drug Piracetam in Binary Solvent Systems

Abstract This study introduces a sustainable reverse-phase liquid chromatography (RPLC) framework to evaluate the retention and pH-dependent ionization of piracetam in conventional and environmentally friendly mobile phases with varying solvent concentrations. The dissociation constant (pKa) of the nootropic drug piracetam was determined from chromatographic data obtained in binary mixtures containing 2-propanol, ethanol, methanol, and acetonitrile at low organic modifier concentrations (1%, 2%, 3%, and 4%, v/v) and in pure water. This data evaluation was performed using nonlinear regression (NLREG) and linear solvation energy relationship (LSER) approaches. Furthermore, to verify the obtained data, chromatographic analyses were conducted under the same conditions on both the XTerra RP18 (250 × 4.6 mm, 5 μm) and Gemini NX C18 (250 × 4.6 mm, 5 μm) columns at 37 °C. The pKa (wwpKa) value of this compound in aqueous medium was estimated indirectly using the macroscopic constant values (mole fraction/dielectric constant) of the relevant organic solvents and was estimated directly in pure water. Furthermore, the sustainability of the studied binary mobile-phase systems was assessed according to the Twelve Principles of Green Analytical Chemistry (GAC) using known metric tools. This article provides the first data on the chromatographic evaluation of piracetam using low-toxicity solvents and significantly reducing chemical waste generation.