Metabolomics-guided valorization of Sicilian Star-Ruby grapefruit (Citrus × paradisi) peels through sustainable microwave-assisted extraction and antioxidant profiling

Grapefruit (Citrus × paradisi) peel is a byproduct whose valorization has frequently relied on microwave-assisted extraction (MAE) to enhance recovery of phenolic compounds and antioxidant potential. Up to now, MAE optimization strategies have largely centered on spectrophotometric indices such as total phenolic content or global antioxidant capacity, providing limited insight into how extraction parameters shape metabolite composition and functional performance. In this study, MAE of residual peel from Star-Ruby grapefruit variety cultivated in Southern Italy was optimized using a multifactorial design-of-experiments (DoE) investigating microwave power (600-1100 W), extraction time (15-40 min), and biomass-to-solvent ratio (1-4 g/100 mL). Extraction efficiency, defined as the cumulative semi-quantitative recovery of structurally characterized secondary metabolites, ranged from 91.33 to 191.22 mg/g dry extract. The fitted quadratic model revealed significant interaction effects, highlighting a non-linear influence of extraction severity on metabolite recovery.To elucidate composition-function relationships, extracts were subjected to targeted and untargeted metabolomic profiling and were evaluated through complementary antioxidant assays. Flavanone glycosides, mainly naringin and narirutin, represented the major fraction of recovered metabolites, while MAE conditions selectively modulated their abundance together with flavonoids, phenolic acids and terpenoid derivatives. Extracts obtained under intermediate conditions exhibited the highest antioxidant performance (e.g., DPPH inhibition ∼17-18 mg TE/g and ABTS inhibition ∼48-49 mg TE/g; CUPRAC: ∼49-50 mg TE/g), whereas milder or more severe conditions resulted in lower or comparable activities despite compositional shifts.Overall, this study provides a mechanistic framework for tailoring phytochemical extraction of residual grapefruit peels through MAE process parameters. The phytochemical and functional data of an Italian pink grapefruit variety further support the targeted valorization of Mediterranean citrus byproducts and may be useful for further development of nutraceutical, functional food, and cosmetic ingredients within a circular bioeconomy strategy.