Hydrophobic natural deep eutectic solvents as a green desorption media for parabens from solid sorbents: A proof-of-concept study

Abstract

A sustainable sample preparation method was developed to determine the concentrations of four parabens (methyl, ethyl, n-propyl, and n‑butyl paraben) in human urine. Initial experiments evaluated three sorbents, C₁₈, PSA, and Florisil®, combined with different methanol and water (MeOH:H₂O) elution strategies. The best performance was achieved using 50 mg of C₁₈ with 500 µL of MeOH:H₂O (80:20, v/v), which was selected as the reference protocol. The method was then redesigned to incorporate a hydrophobic natural deep eutectic solvent (H-NADES) composed of DL-menthol and acetic acid (MAc) in a 1:2 molar ratio as an alternative desorption solvent, along with ultrasound-assisted desorption. A Box–Behnken design was performed to optimise key variables: H-NADES volume, ultrasound time, extraction temperature, and phosphate buffer volume. Other variables, such as HPLC-UV conditions and sorbent type, were evaluated using an univariate approach. The final conditions (200 µL H-NADES and 30 minutes of sonication at 40 °C) provided valuable recoveries. The H-NADES method reduced solvent volume and environmental impact compared to the proposed protocol. The method exhibited good linearity (0.017–50 µg mL^-1), precision (RSD < 10%), and low detection limits (0.006–0.022 µg mL^-1). In addition, green chemistry metrics, AGREE (0.70), AGREEprep (0.48), and ChlorTOX (1.42 g), supported the environmentally friendly performance of the procedure. This work demonstrates that green alternatives based on H-NADES can replace conventional solid-phase protocols using organic solvents, without compromising analytical performance. The developed method offers a simple and eco-friendly approach for an alternative routine biomonitoring of parabens in complex biological matrices.