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LC/MS Methods for Targeted Lipid Analyses Open Access

Descriptions

Other title
Subject/Keyword
lipid
analysis
Lipidomics
LC/MS
quantification
biological samples
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Mi, Si
Supervisor and department
Curtis, Jonathan (Department of Agricultural, Food and Nutritional Science)
Examining committee member and department
Jacobs, Rene (Department of Agricultural, Food and Nutritional Science)
Lehner, Richard (Department of Pediatrics)
Li, Liang (Department of Chemistry)
Griffiths, William (Swansea University Medical School)
Department
Department of Agricultural, Food, and Nutritional Science
Specialization
FOOD SCIENCE AND TECHNOLOGY
Date accepted
2016-09-16T16:14:01Z
Graduation date
2016-06:Fall 2016
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Lipidomics is a research field that attempts to achieve the comprehensive analysis of the entire lipidome in a biological system. The emergence and rapid expansion of lipidomic studies is driven by the great advances in chromatographic separation and mass spectrometry. For this dissertation, I have focused on the development of analytical strategies for targeted and quantitative lipidomics. The targeted lipid and lipid-related compounds include bile acids (including free and conjugated forms), sphingolipids, trimethylamine (TMA) and trimethylamine N-oxide (TMAO) as well as conjugated linolenic acids (CLnA). Quantitative methods were established based on liquid chromatography/ tandem mass spectrometry (LC/MS/MS) techniques. Parenteral nutrition-associated liver disease (PNALD) is a cholestatic liver disease partially caused by developmental immaturity with regards to hepatic bile acids metabolism and transport. Glucagon-like peptide-2 (GLP-2) has been reported to be associated with improved bile flow, and serum and histologic markers of cholestasis. A universal method comprised of C18-based solid-phase extraction (SPE) procedure and LC/MS/MS was developed and validated to monitor the alterations in the bile acids compositions in piglet bile samples in a control group compared to a GLP-2 treated group. As a result, up to 12 different bile acids species were identified in bile sample extracts. Bile acid quantification showed that GLP-2 therapy did improve the clinical phenotype of PNALD by altering bile acids synthesis and transport. Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in North American and European adults. Sphingolipid metabolism is altered in numerous cancers, but strong evidence is still lacking to support this finding in CLL In order to investigate the distributions of sphingolipids in both cancerous and healthy B cells, an LC/MS/MS method along with a single-phase extraction was established. 17 sphingolipid species were successfully detected in the lipid extracts of B cells collected from CLL patients (n=5) and healthy donors (n=4). Quantitative data shows that there was an altered sphingolipid composition (increased levels) observed in the B cells from the CLL patients compared to those from healthy donors. Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are metabolites of choline-related compounds. Abnormal TMA and TMAO concentration levels in biological materials could lead to the occurrence of diseases, such as atherosclerosis and trimethylaminuria. A new HILIC LC/MS/MS method with prior derivatization procedure to TMA enables the simultaneous identification and quantification of TMA and TMAO in mouse plasma samples in a single LC run within 5 min. Conjugated linolenic acid (CLnA) isomers are present in high levels in pomegranate seed oils (PSO) and tung seed oils (TSO). These isomers are considered as health-enhancing compounds and the conjugated unsaturation facilitates the manufacture of organic coatings and polymers. Silver ion liquid chromatography coupled to in-line ozonolysis/mass spectrometry (Ag+-LC/O3-MS) has been proposed for unambiguous identification of CLnA isomers in PSO and TSO samples. Using this novel method, we have achieved the most comprehensive CLnA profiles in PSO and TSO samples reported to date. Overall, the LC/MS-based lipidomic strategies developed in these studies provide us with an informative platform for comprehensive analysis of lipids and lipid-related compounds in various biological samples. The quantitative data collected in lipidomics experiments could be further applied in different areas, such as medical research, pharmaceutical and nutritional studies.
Language
English
DOI
doi:10.7939/R3WS8HX3N
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
S. Mi, D.W. Lim, J.M. Turner, P.W. Wales and J.M. Curtis, “Determination of Bile Acids in Piglet Bile by Solid Phase Extraction and Liquid Chromatography‑Electrospray Tandem Mass Spectrometry”, Lipids, 51 (2016) 359-372.S. Mi, Y-Y Zhao, R.F. Dielschneider, S.B. Gibson and J.M. Curtis, “An LC/MS/MS Method for the Simultaneous Determination of Individual Sphingolipid Species in B Cells”, Journal of Chromatography B, 1031 (2016) 50-60.J.M. Curtis, S. Mi, “Hydrophilic Interaction Liquid Chromatography for Determination of Betaine” (Chapter 10) in: Victor R. Preedy (Ed.), Betaine: Chemistry, Analysis, Function and Effects, RSC publishing, London, 2015, pp. 139-158.D.W. Lim, P.W. Wales, S. Mi, J.Y. Yap, J.M. Curtis, D.R. Mager, V.C. Mazurak, P.R. Wizzard, D.L. Sigalet, J.M. Turner, “Glucagon-Like Peptide-2 Alters Bile Acid Metabolism in Parenteral Nutrition-Associated Liver Disease”, Journal of Parenteral and Enteral Nutrition, 40 (2016) 22-35.R.F. Dielschneider, H. Eisenstat, S. Mi, J.M. Curtis, W. Xiao, J.B. Johnston, S.B. Gibson, “Lysosomotropic Agents Selectively Target Chronic Lymphocytic Leukemia Cells Due to Altered Sphingolipid Metabolism”, Leukemia, 30 (2016) 1290-1300.

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