The use of natural materials and reagents is crucial for developing environmentally friendly methods. This study proposed an excellent green, convenient, cost-effective and rapid sample preparation method called kapok fiber-supported liquid-phase microextraction using natural deep eutectic solvent (KF-SLME-NADES). Natural kapok fiber and NADES were used as greener alternatives to conventional support medium and extractants. Low-toxic ethanol was employed as the desorption solvent. The extraction process was streamlined in a syringe form, allowing for simple pull-push operations. As a proof of concept, the developed methodology was utilized for extracting antidepressants from 3 mL of diluted biological fluids. The optimized KF-SLME-NADES conditions were obtained by single-factor experiments and Box-Behnken design as follows: 2 mg of kapok fiber, 13 μL of NADES composed of menthol and thymol in an equal molar ratio as the extractant, a sampling solution with a pH of 8.0, a desorption solution of 100 μL of ethanol, and four pull-push cycles for both extraction and elution. The validated method provided good linearity (0.05–5.00 μg/mL, R2 > 0.999) and possessed limits of quantification spanning from 0.025 to 0.048 μg/mL. Satisfied accuracies and precisions were obtained with relative recoveries ranging in 93.3–107.2% and intra- and inter-day RSD(%) being below 7.7%. The method greenness was found to be excellent by assessing five greenness evaluation metrics. The devised KF-SLME-NADES strategy provides a sustainable and effective method for bioanalysis.
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