Green ionic liquid-based ultrasound-assisted extraction coupled with UHPLC-MS/MS for platycodin saponins: Density functional theory-elucidated mechanism

This study established an ionic liquid-based ultrasound-assisted extraction (IL-UAE) method coupled with UHPLC-MS/MS to extract and quantify five platycodin saponins from Platycodon grandiflorum . We optimized the extraction conditions using single-factor experiments and a Box-Behnken design (BBD) with response surface methodology. The optimal parameters were 0.8 mol/L [C₄MIM][Br], a liquid-to-solid ratio of 43 mL/g, a 38 °C extraction temperature, a 40 min extraction time, and a 6% NaOH concentration. These conditions yielded a total saponin content of 3.184%. The UHPLC-MS/MS method showed strong linearity ( R² > 0.9993) and reliability, with recoveries ranging from 87.80% to 114.78%. Furthermore, density functional theory (DFT) calculations (including electrostatic potential, independent gradient model based on Hirshfeld partition, and frontier molecular orbital analysis) were applied to clarify the extraction mechanism. DFT results suggested a possible synergistic interaction pattern: Br⁻ contributed to charge redistribution and hydrogen-bonding interactions with platycodin D, while [C₄MIM]⁺ provided a relatively stable solvation environment. The IL-UAE method demonstrated higher extraction efficiency than conventional water and 70% methanol extractions. Multi-metric greenness assessments, highlighted by an AGREE score of 0.8, showed a favorable greenness profile for the proposed protocol. This work provides an efficient and theoretically supported workflow for the extraction and quality control of platycodin saponins in botanical materials.