Research Article

Systematic evaluation of acetone and acetonitrile for use in hydrophilic interaction liquid chromatography coupled with electrospray ionization mass spectrometry of basic small molecules

  1. James Heaton1,
  2. Michael D. Jones1,2,
  3. Cristina Legido-Quigley1,
  4. Robert S. Plumb1,2,
  5. Norman W. Smith1,*

Article first published online: 21 NOV 2011

DOI: 10.1002/rcm.5271

Issue

Rapid Communications in Mass Spectrometry

Rapid Communications in Mass Spectrometry

Volume 25, Issue 24, pages 3666–3674, 30 December 2011

Additional Information

How to Cite

Heaton, J., Jones, M. D., Legido-Quigley, C., Plumb, R. S. and Smith, N. W. (2011), Systematic evaluation of acetone and acetonitrile for use in hydrophilic interaction liquid chromatography coupled with electrospray ionization mass spectrometry of basic small molecules. Rapid Commun. Mass Spectrom., 25: 3666–3674. doi: 10.1002/rcm.5271

Author Information

  1. 1

    Pharmaceutical Science Division, School of Biomedical and Health Sciences, King's College London, London, UK

  2. 2

    Waters Corporation, Milford, MA, USA

*N. W. Smith, Pharmaceutical Science Division, School of Biomedical and Health Sciences, King's College London, 150 Stamford Street, London SE1 9NH, UK.
E-mail: norman.2.smith@kcl.ac.uk

Publication History

  1. Issue published online: 15 NOV 2011
  2. Article first published online: 21 NOV 2011
  3. Manuscript Accepted: 21 SEP 2011
  4. Manuscript Revised: 20 SEP 2011
  5. Manuscript Received: 19 JUL 2011

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Sub-2-µm particle size hydrophilic interaction liquid chromatography [HILIC] combined with mass spectrometry has been increasing in popularity as a complementary technique to reversed-phase LC for the analysis of polar analytes. The organic-rich mobile phase associated with HILIC techniques provides increases in compound ionization, due to increased desolvation efficiency during electrospray ionisation mass spectrometric (ESI-MS) analysis. Although recent publications illustrated selectivity and response comparisons between reversed-phase LC/MS and HILIC LC/MS, there are limited discussions evaluating the optimisation of the mass spectrometry parameters regarding analytes and alternative mobile phases. The use of acetone as an alternative organic modifier in HILIC has been investigated with respect to signal-to-noise in ESI-MS for a variety of polar analytes. Analyte reponses were measured based on a variety of cone and capillary voltages at low and high pH in both acetone and acetonitrile. In order to visualise compound behaviour in the ESI source, surface plots were constructed to assist in interpreting the observed results. The use of acetone in ESI is complicated at low m/z due to the formation of condensation products. Favourable responses were observed for certain analytes and we envisage offering an insight into the use of acetone as an alternative to acetonitrile under certain analytical conditions for particular compound classifications for small molecule analysis. We also highlight the importance of optimising source voltages in order to obtain the maximum signal stability and sensitivity, which are invariably, highly solvent composition dependent parameters. Copyright © 2011 John Wiley & Sons, Ltd.

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