Download the full-sized PDF of Development of Isotope Labeling Methods and Data Processing Program for Liquid Chromatography Mass Spectrometry-Based Metabolome AnalysisDownload the full-sized PDF



Permanent link (DOI):


Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Graduate Studies and Research, Faculty of


This file is in the following collections:

Theses and Dissertations

Development of Isotope Labeling Methods and Data Processing Program for Liquid Chromatography Mass Spectrometry-Based Metabolome Analysis Open Access


Other title
Liquid chromatography
mass spectrometry
Metabolome analysis
Isotope labeling
Type of item
Degree grantor
University of Alberta
Author or creator
Zhou, Ruokun
Supervisor and department
Li, Liang (Department of Chemistry)
Examining committee member and department
Perreault Helene (Department of Chemistry, university of Manitoba)
Campbell, Robert (Department of Chemistry)
Harrison, Jed (Department of Chemistry)
Damaraju, Sambasivarao (Department of Laboratory Medicine and Pathology)
Clive, Derrick (Department of Chemistry)
Department of Chemistry

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Metabolomics strives to gain a comprehensive picture of the metabolites in a biological system. This emerging research field gives us an insight into the discovery of disease-related biomarkers and an understanding of metabolic flux as well as mechanisms. Liquid chromatography mass spectrometry (LC-MS) is one of the leading techniques used in metabolomics owing to its high sensitivity and capability for structure elucidation. The main objective of my research was to develop improved LC-MS based differential isotopic labeling methods to quantify and identify metabolites in biological samples with enhanced analytical performance. First of all, an improved dansylation labeling protocol was developed for profiling amine- and phenol-containing metabolites, which can be used to more efficiently label multiple samples in metabolome analysis. Secondly, a new triplex DIL reagent: 5-diethylamino-naphthalene-1-sulfonyl chloride (DensCl), was developed to increase the sample throughput by at least two-fold, compared to the duplex dansylation labeling approach. Thirdly, a new type of isotope labeling reagent was synthesized to provide a means of chemical structure analysis based on the MS/MS fragmentation patterns generated from the labeled metabolites. Finally, a data processing software, IsoMS, was developed to quickly extract quantitative information from LC-MS data generated by the isotope labeling method. The significance of my research work is that the methods developed can be used to analyze the metabolome with high performance, thereby increasing the application capability of metabolomics for disease biomarker discovery and biological functional studies of metabolites in systems biology.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Zhou, R.; Guo, K.; Li, L. Anal. Chem. 2013, 85, 11532-9.

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 5120490
Last modified: 2015:10:12 20:24:31-06:00
Filename: Zhou_Ruokun_Spring 2014.pdf
Original checksum: 7734b6260c0cd8c4b2b2ab55c4614ab8
Well formed: true
Valid: true
File author: Ruokun Zhou
Page count: 174
File language: en-US
Activity of users you follow
User Activity Date