TIMS-MS combined with theoretical modeling for flavonoid isomer separation using cyclodextrin-metal ion ternary complexes.

In this study, ion mobility mass spectrometry (IM-MS) and theoretical modeling were used to identify flavonoid isomers. MS results showed that the isomers could not be distinguished based on their similar m/z values, fragment ions, or mobility values. β/γ-Cyclodextrin (CD) can interact with the isomers and improve their IM separation, but the peak-to-peak resolution (Rp-p) was limited. Notably, upon the addition of metal ions, α/β/γ-CD all interacted and Rp-p was substantially enhanced, reaching 2.574 in β-CD-Ba2+ system. Theoretical modeling revealed the incorporation of metal ions altered the cavity structure of CD, and differences in interaction sites among the complexes led to structural variations, enabling mobility separation. Quantitative analysis demonstrated good linearity (R2 ≥ 0.99) and a detection limit of 1.31 ng mL-1. The method has been applied in four food samples, with recoveries≥83.51% and RSDs≤4.90%. Overall, this method is simple and highly sensitive, paving an alternative approach for analysis of flavonoid isomers.