Rapid Recognition of Matrine Enantiomers Using Ion Mobility–Mass Spectrometry and Theoretical Modeling with Macrolide as Chiral Selectors

Abstract

The precise analysis of chirality is crucial for elucidating their stereoselective effects. Ion mobility–mass spectrometry (IM-MS) is a promising tool for chirality analysis, yet it is constrained by limited resolving power and the correlation between collision cross-section (CCS) values and accurate structures. In this work, a rapid method for recognizing matrine (MAT) and its enantiomer sophoridine (SPD) was established using IM-MS and theoretical modeling. With Natamycin (Nat) and Amphotericin B (Amp) as chiral selectors, binary noncovalent complexes were formed with target analytes to enhance stereostructural differences and enable separation. MAT and SPD were effectively separated via [MAT/SPD+Nat+H]+ and [MAT/SPD+Amp+H]+ complexes, with peak-to-peak resolutions (Rp–p) of 1.12 and 3.46, yielding 12.2 and 37.6-folds higher than that of free-state enantiomers (0.092), respectively. Theoretical modeling and noncovalent interaction analysis revealed key interaction sites and force types, explaining the differences in mobility behavior at the molecular level. Surface electrostatic potential analysis reveals that smaller CCS values of the complex relate to concentrated negative potential and stronger surface polarity, while larger CCS values lead to dispersed negative potential and weaker polarity. Tandem mass spectrometry confirmed stability variations between isomeric complexes, with larger CCS differences correlating with more significant dissociation energy differences. Applied to practical samples, the method achieved a detection limit of 0.0011 μmol·L–1, recoveries ≥76.00% and relative standard deviations ≤4.62%, and the mechanistic conclusions derived from MAT/SPD can be generalized to other matrine-type alkaloid enantiomers, thereby providing a robust and efficient universal solution for their rapid analysis.