Athina Papadopoulou, Vasiliki Boti, Christina Nannou
This review provides a comprehensive evaluation of recent advances in miniaturized Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) sample preparation techniques applied across food, environmental, and biological matrices. Covering developments within 2020–2025, it focuses on analytical performance, environmental impact, and alignment with principles of sustainable and green analytical chemistry. Central to this review is the significant reduction in solvent and sample volumes achieved through miniaturization, thus decreasing the reagent consumption and hazardous waste generation. The integration of eco-friendly extraction solvents and sorbent materials enhances selectivity and reduces the environmental footprint. These methods are often coupled with high-resolution mass spectrometers, enabling sensitive, multi-residue, and suspect analysis. Challenges associated with complex matrices, low analyte concentrations, and the need for robust clean-up procedures are addressed through innovative hybrid workflows and advanced materials, e.g., polymeric electrospun fibers and deep eutectic solvents. The growing adoption of greener protocols is highlighted. Moreover, it underscores their potential to improve routine analytical workflows while reducing environmental burden. Future research should focus on the development of sustainable sample preparation with improved sensitivity, broader applicability, and minimal ecological impacts. This comprehensive assessment supports the ongoing transformation of analytical chemistry towards more sustainable practices without compromising analytical reliability and efficacy.