Imperial College London
Alternate

Dr Elizabeth Want

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3023e.want

 
 
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Location

 

E315CBurlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chekmeneva:2015:10.1039/C5AY00850F,
author = {Chekmeneva, E and Correia, G and Denes, J and Gomez-Romero, M and Wijeyesekera, A and Perenyi, DR and Koot, Y and Boomsma, C and Want, EJ and Dixon, PH and Macklon, NS and Chan, Q and Takats, Z and Nicholson, JK and Holmes, E},
doi = {10.1039/C5AY00850F},
journal = {Analytical Methods},
pages = {5122--5133},
title = {Development of nanoelectrospray high resolution isotope dilution mass spectrometry for targeted quantitative analysis of urinary metabolites: application to population profiling and clinical studies},
url = {http://dx.doi.org/10.1039/C5AY00850F},
volume = {7},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - An automated chip-based electrospray platform was used to develop a high-throughput nanoelectrospray high resolution mass spectrometry (nESI-HRMS) method for multiplexed parallel untargeted and targeted quantitative metabolic analysis of urine samples. The method was demonstrated to be suitable for metabolic analysis of large sample numbers and can be applied to large-scale epidemiological and stratified medicine studies. The method requires a small amount of sample (5 μL of injectable volume containing 250 nL of original sample), and the analysis time for each sample is three minutes per sample to acquire data in both negative and positive ion modes. Identification of metabolites was based on the high resolution accurate mass and tandem mass spectrometry using authentic standards. The method was validated for 8 targeted metabolites and was shown to be precise and accurate. The mean accuracy of individual measurements being 106% and the intra- and inter-day precision (expressed as relative standard deviations) were 9% and 14%, respectively. Selected metabolites were quantified by standard addition calibration using the stable isotope labelled internal standards in a pooled urine sample, to account for any matrix effect. The multiple point standard addition calibration curves yielded correlation coefficients greater than 0.99, and the linear dynamic range was more than three orders of magnitude. As a proof-of-concept the developed method was applied for targeted quantitative analysis of a set of 101 urine samples obtained from female participants with different pregnancy outcomes. In addition to the specifically targeted metabolites, several other metabolites were quantified relative to the internal standards. Based on the calculated concentrations, some metabolites showed significant differences according to different pregnancy outcomes. The acquired high resolution full-scan data were used for further untargeted fingerprinting and improved the differentiation of
AU  - Chekmeneva,E
AU  - Correia,G
AU  - Denes,J
AU  - Gomez-Romero,M
AU  - Wijeyesekera,A
AU  - Perenyi,DR
AU  - Koot,Y
AU  - Boomsma,C
AU  - Want,EJ
AU  - Dixon,PH
AU  - Macklon,NS
AU  - Chan,Q
AU  - Takats,Z
AU  - Nicholson,JK
AU  - Holmes,E
DO  - 10.1039/C5AY00850F
EP  - 5133
PY  - 2015///
SN  - 1759-9679
SP  - 5122
TI  - Development of nanoelectrospray high resolution isotope dilution mass spectrometry for targeted quantitative analysis of urinary metabolites: application to population profiling and clinical studies
T2  - Analytical Methods
UR  - http://dx.doi.org/10.1039/C5AY00850F
UR  - http://hdl.handle.net/10044/1/45397
VL  - 7
ER  -
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