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Ultra performance liquid chromatography-high resolution mass spectrometry and direct infusion-high resolution mass spectrometry for combined exploratory and targeted metabolic profiling of human urine

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Title: Ultra performance liquid chromatography-high resolution mass spectrometry and direct infusion-high resolution mass spectrometry for combined exploratory and targeted metabolic profiling of human urine
Authors: Chekmeneva, E
Dos Santos Correia, G
Gomez Romero, M
Stamler, J
Chan, Q
Elliott, P
Nicholson, J
Holmes, E
Item Type: Journal Article
Abstract: The application of metabolic phenotyping to epidemiological studies involving thousands of biofluid samples presents a challenge for the selection of analytical platforms that meet the requirements of high-throughput precision analysis and cost-effectiveness. Here, direct infusion nanoelectrospray (DI-nESI)- was compared to an ultra-performance (UPLC)-high resolution mass spectrometry (HRMS) method for metabolic profiling of an exemplary set of 132 human urine samples from a large epidemiological cohort. Both methods were developed and optimised to allow simultaneous collection of high resolution urinary metabolic profiles and quantitative data for a selected panel of 35 metabolites. The total run time for measuring the sample set in both polarities by UPLC-HRMS was of 5 days compared to 9 hours by DI-nESI-HRMS. To compare the classification ability of the two MS methods we performed exploratory analysis of the full-scan HRMS profiles to detect sex-related differences in biochemical composition. Although metabolite identification is less specific in DI-nESI-HRMS, the significant features responsible for discrimination between sexes were mostly the same in both MS-based platforms. Using the quantitative data we showed that 10 metabolites have strong correlation (Pearson’s r > 0.9 and Passing-Bablok regression slope 0.8-1.3) and good agreement assessed by Bland-Altman plots between UPLC-HRMS and DI-nESI-HRMS and thus, can be measured using a cheaper and less sample- and time-consuming method. Only five metabolites showed weak correlation (Pearson’s r< 0.4) and poor agreement due to the overestimation of the results by DI-nESI-HRMS, and the rest of metabolites showed acceptable correlation between the two methods.
Issue Date: 5-Oct-2018
Date of Acceptance: 5-Sep-2018
URI: http://hdl.handle.net/10044/1/64378
DOI: https://dx.doi.org/10.1021/acs.jproteome.8b00413
ISSN: 1535-3893
Publisher: American Chemical Society
Start Page: 3492
End Page: 3502
Journal / Book Title: Journal of Proteome Research
Volume: 17
Issue: 10
Copyright Statement: © 2018 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Sponsor/Funder: National Institutes of Health
National Institutes of Health
National Institutes of Health
Medical Research Council (MRC)
National Institute for Health Research
National Institutes of Health
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 0600 370 D330 1362
60024563 ICL
60045948 ICSTM
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Biochemistry & Molecular Biology
ultra performance liquid chromatography
direct infusion mass spectrometry
metabolic profiling
exploratory analysis
quantitative analysis
high-throughput analysis
ultra-performance liquid chromatography
06 Biological Sciences
03 Chemical Sciences
Publication Status: Published
Open Access location: https://pubs.acs.org/doi/10.1021/acs.jproteome.8b00413
Online Publication Date: 2018-09-05
Appears in Collections:Department of Surgery and Cancer