Instantaneous Differentiation of Functional Isomers via Reactive Flowing Atmospheric Pressure Afterglow Mass Spectrometry

Ambient mass spectrometry (AMS) allows direct desorption and ionization of analytes in real time with minimal-to-no sample preparation. However, it may present inadequate capabilities for differentiating isomers. Here, a reactive flowing atmospheric-pressure afterglow (reactive-FAPA) AMS source is developed for rapid isomer differentiation by derivatization of analytes in real time. The effects of the reactive-FAPA operating conditions on the reagent and product ions were studied and optimized for highly volatile and non-volatile model compounds with different carbonyl functional groups. In addition, two functional isomers of valproic acid (VPA) metabolites, 4-ene VPA and gamma-valprolactone, are successfully differentiated for the first time by incorporating methylamine (MA) reagent vapor into the plasma effluent used for desorption/ionization. Reactive-FAPAMS for 4-ene VPA shows only detectable peaks of the protonated acylation product [M + MA-H2O + H](+), while for.-valprolactone, it shows detectable peaks for both protonated acylation product [M + MA-H2O + H](+) and protonated intermediate [M + MA + H](+). A method for quantitative characterization of mixtures of 4-ene VPA and.-valprolactone is also developed and validated. In addition, reactive-FAPAMS also shows better detection sensitivity compared to nonreactive-FAPAMS for some larger analyte types, such as UV filters and steroids. The limit of detection (LOD) of pregnenolone acetate in reactive-FAPAMS is 310 ng/mL, which is about 10 times better than its LOD in nonreactive-FAPA.

Automated summary

A novel reactive flowing atmospheric-pressure afterglow mass spectrometry source was developed for rapid isomer differentiation in real time, successfully distinguishing two functional isomers of valproic acid metabolites, and improving detection sensitivity for some larger analyte types.