Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasma — Application to clinical and epidemiology cohorts

L. Whiley; L.C. Nye; I. Grant; N. Andreas; K.E. Chappell; M.H. Sarafian; R. Misra; R.S. Plumb; M.R. Lewis; J.K. Nicholson; E. Holmes; J.R. Swann; I.D. Wilson

doi:10.1021/acs.analchem.8b05884

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Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasma — Application to clinical and epidemiology cohorts

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Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasma — Application to clinical and epidemiology cohorts

L. Whiley, L.C. Nye, I. Grant, N. Andreas, K.E. Chappell, M.H. Sarafian, R. Misra, R.S. Plumb, M.R. Lewis, J.K. Nicholson, …

Analytical Chemistry, Vol.91(8), pp.5207-5216

2019

DOI: https://doi.org/10.1021/acs.analchem.8b05884

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Abstract

A targeted ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-ESI-MS/MS) method has been developed for the quantification of tryptophan and its downstream metabolites from the kynurenine and serotonin pathways. The assay coverage also includes markers of gut health and inflammation, including citrulline and neopterin. The method was designed in 96-well plate format for application in multiday, multiplate clinical and epidemiology population studies. A chromatographic cycle time of 7 min enables the analysis of two 96-well plates in 24 h. To protect chromatographic column lifespan, samples underwent a two-step extraction, using solvent protein precipitation followed by delipidation via solid-phase extraction (SPE). Analytical validation reported accuracy of each analyte <20% for the lowest limit of quantification and <15% for all other quality control (QC) levels. The analytical precision for each analyte was 2.1–12.9%. To test the applicability of the method to multiplate and multiday preparations, a serum pool underwent periodic repeat analysis during a run consisting of 18 plates. The % CV (coefficient of variation) values obtained for each analyte were <15%. Additional biological testing applied the assay to samples collected from healthy control participants and two groups diagnosed with inflammatory bowel disease (IBD) (one group treated with the anti-inflammatory 5-aminosalicylic acid (5-ASA) and one group untreated), with results showing significant differences in the concentrations of picolinic acid, kynurenine, and xanthurenic acid. The short analysis time and 96-well plate format of the assay makes it suitable for high-throughput targeted UHPLC-ESI-MS/MS metabolomic analysis in large-scale clinical and epidemiological population studies.

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Title: Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasma — Application to clinical and epidemiology cohorts
Authors/Creators: L. Whiley (Author/Creator) - UK Dementia Research Institute
L.C. Nye (Author/Creator) - Imperial College London
I. Grant (Author/Creator) - Imperial College London
N. Andreas (Author/Creator) - Imperial College London
K.E. Chappell (Author/Creator) - Hammersmith Hospital
M.H. Sarafian (Author/Creator) - Imperial College London
R. Misra (Author/Creator) - St. Marks Hospital and Academic Institute , Watford Road , Middlesex, London HA1 3UJ , United Kingdom.
R.S. Plumb (Author/Creator) - Waters (United States)
M.R. Lewis (Author/Creator) - Hammersmith Hospital
J.K. Nicholson (Author/Creator) - Murdoch University
E. Holmes (Author/Creator) - UK Dementia Research Institute
J.R. Swann (Author/Creator) - Imperial College London
I.D. Wilson (Author/Creator) - Imperial College London
Publication Details: Analytical Chemistry, Vol.91(8), pp.5207-5216
Publisher: American Chemical Society
Identifiers: 991005541025307891
Copyright: © 2019 American Chemical Society
Murdoch Affiliation: Australian National Phenome Centre; Centre for Computational and Systems Medicine
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.231 Vitamin Metabolism; 1.231.1938 Tryptophan Metabolism
Web Of Science research areas: Chemistry, Analytical
ESI research areas: Chemistry