A novel hydrogen-incorporated carbon dioxide supercritical system for extracting phytochemicals from grape peels: Response surface methodology–based modeling and optimization

• Sp-CO₂-H₂ method enables selective enrichment of phytochemicals rather than solely increasing total phenolic content (TPC) • The highest TPC (33.75 mg GAE/100 mL), DPPH (62.02%), and ABTS (65.47%) were obtained at 80 bar, 60 °C, and 5 min • Moderate RSM model performance can still provide reliable optimization outcomes in complex multi-response extraction systems • Multivariate analyses reveal a consistent decoupling between total phenolic content and antioxidant activity • PCA and correlation patterns support selective extraction behavior under optimized Sp-CO₂–H₂ conditions • Sp-CO₂–H₂ increased the TPC, DPPH, and ABTS of extracts by 55%, 44%, and 24%, respectively, compared to the classical Sp-CO 2 method The supercritical hydrogen-incorporated carbon dioxide (Sp-CO 2 –H 2 ) extraction was evaluated as a hybrid solvent system for the recovery of phytochemicals from grape peels, utilizing response surface methodology (RSM), mathematical modelling, and optimization techniques. The independent variables (pressure, temperature, and time) were optimized using RSM for total phenolic content (TPC), antioxidant activity, and individual phenolic compound levels. The optimum Sp-CO 2 –H 2 conditions were determined as 80 bar, 60 °C, and 5 min. The developed RSM models showed acceptable performance, with coefficients of determination (R²) ranging from moderate to high values and statistically significant model terms (P<0.05), while lack-of-fit was not significant. Model validation demonstrated that the experimental results agreed with the predicted values, with percentage uncertainty (U%) values generally below 26%. Under the optimized conditions, TPC and antioxidant activity reached their highest levels. Multivariate analyses indicated that the optimized parameters clustered together with bioactive properties in PCA, and this behavior was further supported by clustering patterns observed in the heatmap. The Sp–CO 2 –H 2 method is more efficient for extracting phenolic compounds and antioxidants from Cimin grape peels than the classical Sp-CO 2 method, with an increase in TPC, DPPH, and ABTS values of extracts by 55%, 44%, and 24%, respectively. Overall, the optimization and modelling results suggest that the Sp-CO 2 –H 2 system is an effective and reliable approach for the selective extraction of phytochemicals from grape peels, likely by favoring selective enrichment and preservation of antioxidant-active constituents rather than by directly increasing total phenolic yield.