Exploring Caffeine Extraction Using Hydrophobic Deep Eutectic Solvents: Experimental and Theoretical Approaches

Hydrophobic deep eutectic solvents (HDESs) are emerging as sustainable, biodegradable, and nontoxic alternatives to traditional organic solvents in liquid–liquid extraction processes. This study investigates the use of HDESs, specifically eutectic mixtures of dl-menthol combined with acetic or hexanoic acids, for extracting caffeine from coffee beans (CB), coffee skin (CS), and guaraná drink (GD). Solvent screening using COSMO-RS modeling was performed to identify effective HDES systems. Caffeine detection employed UV/vis spectrophotometry at 274 nm (dl-menthol/acetic acid system) and 284 nm (dl-menthol/hexanoic acid system), with application of Gaussian fitting to minimize spectral interferences. The optimal extraction conditions were determined to be 65 °C and a 1:1 initial solution to solvent (L/L) ratio. Under these conditions, the dl-menthol/acetic acid solvent extracted 0.765 ± 0.007 mg of caffeine per 100 mg of coffee beans, outperforming the dl-menthol/hexanoic acid solvent, which extracted 0.610 ± 0.010 mg. Comparable results were observed for the other matrices, with 0.66 ± 0.01 mg caffeine per 400 mg of coffee skin and 0.57 ± 0.01 mg per 10 mL of guaraná drink. The method presented high precision, with a standard deviation of ±0.0826 mg L^–1 for five measurements of a 15 mg L^–1 caffeine solution, and detection and quantification limits of 0.674 and 2.04 mg L^–1, respectively. The sustainability of the method was evaluated using the AGREE (Analytical GREEnness) metric, obtaining a high greenness score of 0.83, exceeding the values for traditional solvents such as dichloromethane and chloroform. These findings demonstrated the potential of HDESs as greener, safer, and more efficient alternatives for caffeine extraction, aligning with green chemistry principles and supported by both experimental and theoretical evaluations.