Trapped ion mobility spectrometry - mass spectrometry analysis and computational modeling of noncovalent α-, β-, and...

Vitamin C is highly susceptible to oxidative and thermal degradation, limiting its shelf life and bioavailability in pharmaceutical and food formulations. Cyclodextrins are commonly employed to enhance the stability of such labile compounds through noncovalent inclusion complexation. However, the ability of α-, β-, and γ-cyclodextrins to stabilize vitamin C varies due to differences in cavity size and binding interactions. Understanding these interactions is essential for selecting the most suitable carrier. This study hypothesizes that the stability and conformational behavior of vitamin C-cyclodextrin complexes can be comprehensively evaluated using a combination of analytical techniques. The complexes were analyzed using the trapped ion mobility spectrometry-time-of-flight-mass spectrometry. MS/MS survival yield curves enabled comparison of gas-phase stabilities. DFT calculations provided insights into interaction energies and geometries. The data show that α-cyclodextrin is too small, γ-cyclodextrin forms less stable complexes, and β-cyclodextrin shows optimal encapsulation. These findings support rational excipient selection in formulation development.