Valorization of wheat-derived pharmaceutical waste via sustainable NADES-based extraction and untargeted bioactive profiling

The production of the aqueous extract of wheat ( Triticum vulgare) , known for its tissue repair properties, generates significant solid waste, with no identified reuse. Traditional extraction techniques, using organic solvents, are widely used for their efficiency, but present disadvantages, as long extraction times and high consumption of organic solvents, often toxic and environmentally harmful. To overcome these limitations and reduce environmental impact, new-generation solvents, such as natural deep eutectic solvents (NADES), have recently emerged. This study investigates the extraction efficiency of NADES for recovering bioactive compounds from wheat-based waste using both targeted and untargeted analytical approaches. Eight NADES formulations with varying physicochemical properties (pH, polarity, and viscosity) were evaluated. The extraction efficiency was assessed through ferulic acid recovery analysis by UHPLC-Q-ToF-HRMS. The highest recovery was achieved using a NADES composed of betaine:1,3-butanediol:water (molar ratio, 1:3:10.6), attributed to its moderate pH, low viscosity, and water content. The key parameters of the ultrasound-assisted extraction were optimized using Response Surface Methodology (RSM). Results showed that the extraction yield was comparable to that obtained using a conventional hydroalcoholic mixture, while non-targeted analysis revealed the presence of different bioactive compounds depending on the extraction solvent. The optimized method was assessed for greenness and applicability through AGREEprep and BAGI metrics, compared with hydroalcoholic extraction approaches. This study highlights the potential of wheat-based waste as a valuable source of ferulic acid and other bioactive compounds, demonstrating the feasibility of NADES as a sustainable alternative to traditional solvents for producing ready-to-use extracts suitable for nutraceutical and pharmaceutical applications. • Hydrophilic/hydrophobic NADES were tested for wheat pharmaceutical waste extraction. • Betaine:1,3-butanediol:water (1:3:10.6) achieved highest ferulic acid yield. • Multivariate optimization of NADES-based UAE parameters using design of experiments. • Untargeted HRMS revealed distinct bioactive profiles vs hydroalcoholic extracts. • Greenness and practicability were validated by AGREEprep and BAGI metrics.