Eco-Friendly Reversed-Phase Liquid Chromatography Methods Using Alternative Solvents for Pharmaceutical Analysis

Abstract: Traditional solvents, such as acetonitrile and methanol, are widely used in reversed-phase liquid chromatography (RPLC), but their toxicity, flammability, and improper disposal contribute significantly to environmental and health hazards. These solvents pollute soil, water, and air, which are toxic to ecosystems and pose a potential risk to the human food chain. This re-view aims to explore green RPLC methods as environmentally sustainable alternatives to conven-tional chromatographic methods, with a focus on replacing toxic solvents with green alternatives such as ethanol, water, ionic liquids, deep eutectic solvents, and bio-based solvents. These green solvents are aligned with the principles of green chemistry because of their lower toxicity, mini-mal environmental footprints, and their ability to improve overall sustainability. Methodological strategies like factorial design and Six Sigma approaches are used to optimise key chromato-graphic parameters such as mobile phase, stationary phase, pH, column temperature, and elution mode. These allow green RPLC approaches to achieve performance comparable to conventional systems in terms of sensitivity, selectivity, accuracy, and resolution. Green analytical chemistry metrics such as NEMI, Eco-Scale, and GAPI are used to quantify the environmental sustainability of analytical approaches. Validated case studies show the effective use of green solvents in phar-maceutical analysis according to regulatory requirements of reproducibility and reliability. Life Cycle Assessment (LCA) also confirms that green RPLC strategies minimize waste, energy con-sumption, and carbon footprint by a great extent. This shift towards sustainable chromatographic practices is a significant milestone in pharmaceutical analysis, maintaining the ecology without compromising analytical integrity.