Multi-criteria sustainability assessment of deep eutectic solvent-based liquid-liquid microextraction for prostate cancer therapeutics: Green, practical, and innovative approach

• First use of terpene-based DES in VA-LLME of flutamide and finasteride. • Systematic optimization of the significant variables using a univariate strategy. • Low LODs of 0.016 and 0.033 µg/mL for flutamide and finasteride, respectively. • The method was successfully applied to plasma and river water. • A holistic evaluation of greenness, practicality, performance, and innovation was performed. This study presents the first application of a terpene-based deep eutectic solvent (DES) in liquid-liquid microextraction (LLME) of flutamide (FTM) and finasteride (FSR) prior to HPLC-DAD analysis. The extraction efficacy was optimized through systematic evaluation of key parameters, including DES type and volume, vortex time, ionic strength, and pH. Under the optimal conditions, the method demonstrated acceptable linearity over the concentration range of 0.05–15 and 0.10–10 µg/mL with limits of detection (LODs) of 0.016 and 0.033 µg/mL for FTM and FSR, respectively. The precision, expressed as %RSDs, was <3.5 %, demonstrating high repeatability and reproducibility. Furthermore, the method was successfully applied to spiked human plasma and river water samples, yielding recovery rates between 97 and 102 %, confirming its reliability in complex matrices. Finally, a comprehensive multi-criteria sustainability assessment using eight metrics highlighted the method's outstanding greenness, practicality, performance, and innovation. This study explores the potential of terpene-based DESs as sustainable extraction solvents for enhanced pharmaceutical and environmental analysis.