Favorable Effects of Weak Acids on Negative-Ion Electrospray Ionization Mass Spectrometry

Abstract

Despite widespread use in pharmacokinetic, drug metabolism, and pesticide residue studies, little is known about the factors governing response during reversed-phase liquid chromatography coupled with negative-ion electrospray ionization (ESI(-)) mass spectrometry. We examined the effects of various mobile-phase modifiers on the ESI(-) response of four selective androgen receptor modulators using a postcolumn infusion system. Acetic, propionic, and butyric acid improved the ESI(-) responses of analytes to varying extents at low concentrations. Formic acid suppressed ionization, as did neutral salts (ammonium formate, ammonium acetate) and bases (ammonium hydroxide, triethylamine) under most conditions. Two modifiers (2,2,2-trifluoroethanol, formaldehyde) that produce anions with high gas-phase proton affinity increased ESI(-) responses. However, the concentrations of these modifiers required to enhance ESI(-) response were higher than that of acidic modifiers, which is a phenomenon likely related to their low pK(a) values. 2,2,2-Trifluoroethanol increased response of more hydrophobic compounds but decreased response of a more hydrophilic compound. Formaldehyde improved response of all the compounds, especially the hydrophilic compound with lower surface activity. In summary, these results suggest that an ideal ESI(-) modifier should provide cations that can be easily electrochemically reduced and produce anions with small molecular volume and high gas-phase proton affinity.

Relative importance of basicity in the gas phase and in solution for determining selectivity in electrospray ionization mass spectrometry

“…For our studies, acetic acid was employed for acidification to circumvent the problem of signal suppression. Other investigators have previously observed changes in electrospray response upon acidifying the analyte solution with acetic acid [17,18]. The studies presented here are, however, unique in that the observed responses in acidified and neat methanol are compared with the calculated concentration of the protonated form of the analyte in each solution.…”

ESI‐MS investigation of solvent effects on the chiral recognition capacity of tartar emetic towards neutral side‐chain amino acids

“…It was assumed that utility of 75% of the organic modifiers in these solutions were sufficient to represent their effect to these chiral molecular recognition systems. Formaldehyde incorporation (100 mM) to enhance spectral quality of previously reported experiments was not practiced in these experiments, 28,32 because the study was focused on studying the effects by electrospray friendly organic solvent modifiers on these chiral recognition systems. It was assumed that formaldehyde incorporation with a high concentration (100 mM) would influence the solvent properties and alter the original form of the solvent system.…”

Selective Ionization of 2,4-Xylenol in Mass Spectrometry Using a Tunable Laser and Supersonic Jet Technique

“…3 Gas chromatography combined with mass spectrometry (GC/MS) and liquid chromatography combined with mass spectrometry (LC/MS) have been utilized for the analysis of insecticides and pesticides in water. [4][5][6][7][8][9][10] Due to the high solubility of xylenols and their isomers of ethylphenols, LC/MS was tried, but was unsuccessful in separating these chemical species. Analyses of these compounds using GC/MS have been reported elsewhere.…”