Vacuum Ultraviolet-Assisted Electrospray Ionization: Synergistic Protonation Enhancement for Sensitive Analysis of Volatile Aroma Compounds

A vacuum ultraviolet-assisted electrospray ionization (VUV-ESI) hybrid ionization source was developed by orthogonally coupling 124 nm photons to the electrospray plume to enhance the ionization of moderately polar and nonpolar analytes. Using five representative volatile aroma compounds as model analytes, the VUV-ESI system produced signal enhancements of up to 46-fold relative to conventional electrospray ionization. Mechanistic analyses indicate that this enhanced ionization efficiency arises from a synergistic combination of VUV-induced solvent processes and analyte-dependent photoactivation. Specifically, VUV irradiation promotes the formation of protonated solvent clusters that sustain efficient proton-transfer reactions. Concurrently, near-resonant excitation transiently increases the proton affinity of target analytes to favor proton capture, while molecules with relatively low ionization potentials undergo direct single-photon ionization followed by rapid solvent-mediated hydrogen abstraction. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations support this analyte-dependent modulation, revealing excitation-induced increases in apparent proton affinity, exemplified by a 19.04 kcal/mol enhancement for azulene. Under optimized conditions, VUV-ESI demonstrated robust quantitative performance with coefficients of determination (R2) ≥ 0.99 and limits of detection down to 12.5 nmol/L. The method also exhibited reliable spike recoveries in complex Baijiu and essential oil matrices. These results establish the VUV-ESI hybrid source as a highly effective analytical platform for overcoming inherent ionization biases and expanding the accessible analyte coverage in mass spectrometry.