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Advances in quadrupole and time-of-flight mass spectrometry for peptide MRM based translational research analysis

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journal contribution
posted on 05.06.2018 by Richard J. Mbasu, Liam Heaney, Billy J. Molloy, Chris J. Hughes, Leong L. Ng, Johannes P.C. Vissers, James I. Langridge, Donald J.L. Jones
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The application of unit resolution tandem quadrupole and high-resolution orthogonal acceleration ToF mass spectrometers for the quantitation and translational analysis of proteolytic peptides is described. The MS platforms were contrasted in terms of sensitivity and linear response. Moreover, the selectivity of the platforms was investigated and the effect on quantitative precision studied. Chromatographic LC conditions, including gradient length and configuration, were investigated with respect to speed/throughput, while minimizing isobaric interferences, thereby providing information with regard to practical sample cohort size limitations of LC-MS for large cohort experiments. In addition to these fundamental analytical performance metrics, precision and linear dynamic ranges were also studied. An LC-MS configuration that encompasses the best combination of throughput and analytical accuracy for translational studies was chosen, despite the MS platforms giving similar quantitative performance, and instances were identified where alternative combinations were found to be beneficial. This configuration was utilized to demonstrate that proteolytically digested nondepleted samples from heart failure patients could be classified with good discriminative power using a subset of proteins previously suggested as candidate biomarkers for cardiovascular diseases.

Funding

This work was partly supported by the John and Lucille van Geest Foundation and the National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit.

History

School

  • Sport, Exercise and Health Sciences

Published in

Proteomics

Volume

16

Issue

15-16

Pages

2206 - 2220

Citation

MBASU, R.J. ...et al., 2016. Advances in quadrupole and time-of-flight mass spectrometry for peptide MRM based translational research analysis. Proteomics, 16(15-16), pp. 2206-2220.

Publisher

© Wiley

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2016-05-23

Notes

This is the peer reviewed version of the following article: MBASU, R.J. ...et al., 2016. Advances in quadrupole and time-of-flight mass spectrometry for peptide MRM based translational research analysis. Proteomics, 16(15-16), pp. 2206-2220., which has been published in final form at https://doi.org/10.1002/pmic.201500500. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

ISSN

1615-9853

eISSN

1615-9861

Language

en

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