Electrospray Ionization Efficiency Is Dependent on Different Molecular Descriptors with Respect to Solvent pH and Instrumental Configuration

Abstract

Over the past decades, electrospray ionization for mass spectrometry (ESI-MS) has become one of the most commonly employed techniques in analytical chemistry, mainly due to its broad applicability to polar and semipolar compounds and the superior selectivity which is achieved in combination with high resolution separation techniques. However, responsiveness of an analytical method also determines its suitability for the quantitation of chemical compounds; and in electrospray ionization for mass spectrometry, it can vary significantly among different analytes with identical solution concentrations. Therefore, we investigated the ESI-response behavior of 56 nitrogen-containing compounds including aromatic amines and pyridines, two compound classes of high importance to both, synthetic organic chemistry as well as to pharmaceutical sciences. These compounds are increasingly analyzed employing ESI mass spectrometry detection due to their polar, basic character. Signal intensities of the peaks from the protonated molecular ion (MH+) were acquired under different conditions and related to compound properties such as basicity, polarity, volatility and molecular size exploring their quantitative impact on ionization efficiency. As a result, we found that though solution basicity of a compound is the main factor initially determining the ESI response of the protonated molecular ion, other factors such as polarity and vaporability become more important under acidic solvent conditions and may nearly outweigh the importance of basicity under these conditions. Moreover, we show that different molecular descriptors may become important when using different types of instruments for such investigations, a fact not detailed so far in the available literature.

Fig 1. ESI response of aniline and 4-aminopyridine in presence of different, pH-modifying electrolytes.

Analyses carried out a) by syringe pump infusion in 50% ACN on the API 2000, b) by sample flow injection in 50% ACN on the Esquire 3000+ and c) by sample flow injection in 80% ACN on the Esquire 3000+.

Fig 2. Response ratio of the ESI signal intensity at pH 3 and pH 7 in dependency on basicity.

The response of every analyte in aqueous solution (pH 7) is compared to a solution adjusted to pH 3 by formic acid, analyzed for the whole set of analytes in 80% ACN on the API 2000.

Fig 3. Signal enhancement by solvent acidification.

Enhancement is more pronounced for compounds with lower boiling points. Response ratio pH 3 / pH 7 plotted over the boiling point, double logarithmic graph.