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

Zengru Wu, Wenqing Gao, Mitch A. Phelps, Di Wu, Duane Miller, James T. Dalton

Research output: Contribution to journalArticle

133 Citations (Scopus)

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 pKa 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.

Original languageEnglish (US)
Pages (from-to)839-847
Number of pages9
JournalAnalytical Chemistry
Volume76
Issue number3
DOIs
StatePublished - Feb 1 2004

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formic acid
Trifluoroethanol
Electrospray ionization
Formaldehyde
Anions
Mass spectrometry
Protons
Negative ions
Gases
Ammonium Hydroxide
Pesticide Residues
Acids
Pharmacokinetics
Liquid chromatography
Androgen Receptors
Metabolism
Acetic Acid
Modulators
Ionization
Cations

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry

Cite this

Favorable Effects of Weak Acids on Negative-Ion Electrospray Ionization Mass Spectrometry. / Wu, Zengru; Gao, Wenqing; Phelps, Mitch A.; Wu, Di; Miller, Duane; Dalton, James T.

In: Analytical Chemistry, Vol. 76, No. 3, 01.02.2004, p. 839-847.

Research output: Contribution to journalArticle

Wu, Zengru ; Gao, Wenqing ; Phelps, Mitch A. ; Wu, Di ; Miller, Duane ; Dalton, James T. / Favorable Effects of Weak Acids on Negative-Ion Electrospray Ionization Mass Spectrometry. In: Analytical Chemistry. 2004 ; Vol. 76, No. 3. pp. 839-847.
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