Imperial College London

Emeritus ProfessorJeremyNicholson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Whiley:2019:10.1021/acs.analchem.8b05884,
author = {Whiley, LW and Nye, L and Grant, I and Andreas, N and Chappell, K and Sarafian, MHS and Misra, R and Plumb, R and Lewis, M and Nicholson, J and Holmes, E and Swann, J and Wilson, I},
doi = {10.1021/acs.analchem.8b05884},
journal = {Analytical Chemistry},
pages = {5207--5216},
title = {Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasmaapplication to clinical and epidemiology cohorts},
url = {http://dx.doi.org/10.1021/acs.analchem.8b05884},
volume = {91},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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.
AU - Whiley,LW
AU - Nye,L
AU - Grant,I
AU - Andreas,N
AU - Chappell,K
AU - Sarafian,MHS
AU - Misra,R
AU - Plumb,R
AU - Lewis,M
AU - Nicholson,J
AU - Holmes,E
AU - Swann,J
AU - Wilson,I
DO - 10.1021/acs.analchem.8b05884
EP - 5216
PY - 2019///
SN - 0003-2700
SP - 5207
TI - Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasmaapplication to clinical and epidemiology cohorts
T2 - Analytical Chemistry
UR - http://dx.doi.org/10.1021/acs.analchem.8b05884
UR - http://hdl.handle.net/10044/1/69044
VL - 91
ER -