The relationship between the electrospray ionization (ESI)-mass spectrometric (MS) response of an analyte and its concentration has been well studied for permanently charged and basic analytes in the positive ionization mode, but there has been a lack of research effort for other analytes, and for the negative ionization mode, in general. In this study, this relationship was investigated for various adducts and deprotonated species of glucose, sucrose, and raffinose using a continuous stirred tank reactor (CSTR) coupled with ESI-tandem MS to obtain a continuum of response factors across a wide concentration range in both the positive and negative ionization modes with a single injection under 18 different combinations of solvents and additives. Profiles of response factors vs. concentrations varied widely and were dependent upon the analyte and solvent parameters. The use of ammonium trifluoroacetate resulted in the highest response factors for methanol-based and acetonitrile-based solvents in the positive and negative ionization modes, respectively. Ammonium acetate, ammonium formate, and sodium chloride in 80:20 acetonitrile:water in the negative ionization mode resulted in good linearities, useful for quantitative analysis. In the positive ionization mode, response factors tended to increase with an increase in the molecular weight of the analyte, and acetonitrile was generally found to decrease response factors. We have also demonstrated the ability of CSTR-ESI-MS to visualize ionization suppression in the presence of co-analytes. These data should be useful for liquid chromatography-ESI-MS method development for sugar analysis, to help guide the choice of mobile phase that will result in high sensitivity and linearity. Graphical Abstract.
Keywords: Carbohydrates; Continuous stirred tank reactor; Electrospray ionization; Saccharides; Solvent effects; Sugars.