RESUMO
The relative contributions to ionization efficiency by three molecular chemical properties have been examined for field-free and field-enabled capillary vibrating sharp-edge spray ionization (cVSSI) using mass spectrometry (MS) analysis. Ion intensities have been recorded for model compounds under each operational ionization mode as well as for aqueous and nonaqueous (methanol) solvent systems. Multiple regression analysis suggests that for field-free cVSSI, ion intensity is mostly associated with the log of the base dissociation constant (pKb) and proton affinity (PA) for both aqueous and methanol solutions. Comparatively, for field-enabled cVSSI using aqueous solutions, the dominant factor correlated with ion intensity is the log of the partition coefficient (log P). To a lesser degree, this is observed for methanol solutions as well. For ESI, pKb is the dominant factor associated with ion signal levels from methanol and aqueous solutions. These results are supported by studies conducted on two different mass spectrometers employing different cVSSI emitter tips. The relationship of ion intensity and pKb in ESI is supported by multiple studies; however, the shift to other chemical properties with the addition of cVSSI suggests the possibility that a different (or combinations of) ionization mechanism(s) may be operative for these ionization modes. These results are briefly considered in light of the different ESI mechanisms.
RESUMO
Rapid, solution-phase hydrogen/deuterium exchange (HDX) coupled with mass spectrometry (MS) is demonstrated as a means for distinguishing small-molecule metabolites. HDX is achieved using capillary vibrating sharp-edge spray ionization (cVSSI) to allow sufficient time for reagent mixing and exchange in micrometer-sized droplets. Different compounds are observed to incorporate deuterium with varying efficiencies resulting in unique isotopic patterns as revealed in the MS spectra. Using linear regression techniques, parameters representing contribution to exchange by different hydrogen types can be computed. In this proof-of-concept study, the exchange parameters are shown to be useful in the retrodiction of the amount of deuterium incorporated within different compounds. On average, the exchange parameters retrodict the exchange level with ~ 2.2-fold greater accuracy than treating all exchangeable hydrogens equally. The parameters can be used to produce hypothetical isotopic distributions that agree (± 16% RMSD) with experimental measurements. These initial studies are discussed in light of their potential value for identifying challenging metabolite species.
