Challenges in achieving a fundamental model for ESI

Abstract

The relative intensities of the ions in an electrospray ionization (ESI) mass spectrum typically do not reflect the relative concentrations of the ions in solution. A partitioning equilibrium model was developed to explain in quantitative detail many of the behaviors observed in ESI in terms of matrix effects. The fundamental experiments required to validate this model presented several challenges in terms of instrumentation, interpretation, and application. The most basic requirement is a stable spray current that can be measured with accuracy and precision since several factors depend on the spray current. Modifications to the instrument used for these experiments resulted in a stable spray current that could be measured accurately, minimum drifting of the total ion current (TIC), and removal of risking damage to the instrument if arcing occurs. The presence of multiple analyte and electrolyte peaks due to fragment and cluster ions, in addition to solvent and impurity ion peaks, require care in distinguishing and accounting for each component in the solution. The dependence of the spray current on several parameters (analyte and electrolyte concentrations, flow rate, needle voltage, and needle position) as well as the interdependencies among these parameters presented other challenges. The limited the range of variability of each parameter due to these interdependencies was extended by extending the range of stability of the spray current by replacing the metal needle with a glass capillary needle. Overcoming these challenges has enabled us to carry out the quantitative fundamental experiments required to establish a working ESI model with broad applications.