Think Negative: Finding the Best Electrospray Ionization/MS Mode for Your Analyte

Abstract

For the first time, the electrospray ionization efficiency (IE) scales in positive and negative mode are united into a single system enabling direct comparison of IE values across ionization modes. This is made possible by the use of a reference compound that ionizes to a similar extent in both positive and negative modes. Thus, choosing the optimal (i.e., most sensitive) ionization conditions for a given set of analytes is enabled. Ionization efficiencies of 33 compounds ionizing in both modes demonstrate that, contrary to general practice, negative mode allows better sensitivity for 46% of such compounds whereas the positive mode is preferred for only 18%, and for 36%, the results for both modes are comparable.

Influence of the amino acid composition on the ionization efficiencies of small peptides

“…The significant similarities to previously observed trends allowed suggesting that ionization efficiency can be predicted for the amino acids with a similar model. In order to test this, we predicted the log IE values of all of the amino acids using a previously developed model . The correlation between the predicted and measured values was high (for amino acids R 2 = 0.61, s = 0.55).…”

“…Previously developed model was used to predict the ionization efficiency values of the amino acids and to confirm its applicability to amino acids (Figures , S1, and S2). A good prediction power for predicting log IE values ( s = 0.55) was observed.…”

“…Correlation of measured and predicted log IE values of amino acids (in blue) calculated by the prediction model: log IE = (1.39 ± 0.23) α + (0.36 ± 0.05) WANS + (4.01 ± 0.27); black line depicts the ideal correlation (slope = 1, intercept = 0) [Colour figure can be viewed at wileyonlinelibrary.com]…”

“…As solvent 80/20 acetonitrile (high performance liquid chromatography [HPLC] grade, J. T. Baker, Deventer, Netherlands)/0.1% formic acid (≥98%, Sigma, Steinheim, Germany) in water (ultrapure, 18.2 MΩ cm, TOC 1‐2 ppb, prepared by a Millipore Milli‐Q Advantage A10 water purification system) was used. The anchor compound was tetraethylammonium perchlorate (Fluka, Buchs, Switzerland), log IE = 3.95 (see the anchoring procedure and calculation equations in Liigand et al). Isotope corrections (IC) are used to account for the signals of all the isotopes of the compound.…”

“…Our group has previously focused on predicting the ionization efficiencies of small molecules (mostly compounds with the molecular weight below 400 Da), which ionize via IEM. The physicochemical parameters for the model have been calculated by combining density functional theory (DFT) and COnductor like Screening MOdel for Real Solvents (COSMO‐RS) calculations . In this study, we develop the ionization efficiency model further towards oligopeptides (up to 14 amino acid residues), which are expected to ionize via CEM.…”