Processes that affect electrospray ionization-mass spectrometry of nucleobases and nucleosides

Due to the complexity of electrospray ionization processes and the many factors that affect the ion signal, optimization of electrospray ionization methods to gain ultimate sensitivity for analysis of nucleobases and nucleosides may not be straightforward. In this work, we investigated the effect of the pK _a and the gas-phase basicity of analyte and other electrolytes on the M+H]⁺ ion signal for 11 select nucleobases and nucleosides in 50% methanol:water solution. Solution chemistry plays a role in the electrospray signal for all analytes, but gas-phase chemistry may be important for compounds with pK _a <3 depending on the solution composition. For compounds with pK _a <3, gas-phase proton transfer reactions can be promoted to increase analyte electrospray response by the addition of ammonium acetate to the solution.