Author

Tsz Shan Lum

Year of Award

2016

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Department of Chemistry.

Principal Supervisor

Leung, Kelvin S. Y.

Keywords

Analysis;Drugs;Mass spectrometry

Language

English

Abstract

Elemental detection is an emerging area in bioanalysis. Thanks to the rapid advancement in instrumentation such as inductively coupled plasma-mass spectrometry (ICP-MS), low detection limit and quick analysis can be achieved. Besides, ICP-MS also suffers less matrix effect as compared to molecular mass spectrometry, so a precise and accurate detection of toxic or essential elements can be provided. Different types of sample introduction or separation systems such as laser ablation (LA) and liquid chromatograph (LC) are excellent hyphenation options for the elemental detection apart from the total analysis of standalone ICP-MS analysis. Spatial analysis and speciation of the two mentioned techniques provide additional merits to the elemental detection in bioanalysis.;LA-ICP-MS makes use of a laser to ablate the solid sample, and the generated sample aerosol is then transferred to ICP-MS for detection. It can be used for bioimaging. There are examples of LA mapping of biological tissues to reveal the spatial distribution of metal, to study the neurodegenerated disease in brain or the accumulation in metallodrug in tumor mass. In order to incorporate the imaging tool in drug development, in the first part of this thesis, LA-ICP-MS bioimaging of liver and kidney was performed to compare the differential spatial distribution of two structurally different platinum-based anti-cancer drug candidates. It was expected that this approach can assist the chemical modification in drug development.;To put this idea a step further, the spatial analysis tool was tested for its potential in therapeutic drug monitoring. Hair profiling in whiskers of mice treated with vanadium anti-diabetic complex or gadolinium-based contrasting agents at different dosage levels were conducted. Results shown that different deposition behaviors and accumulation/elimination profile can be observed, demonstrating a great potential in routine clinical application.;On the other hand, LC-ICP-MS offers the possibility for speciation study. Several accessories for organic solvent introduction in ICP-MS make the coupling of reverse phase chromatography using high percentage of organic solvent in the mobile phase more convenient. To demonstrate the advantage of this configuration, a speciation of bromine-containing drug in mice urine and plasma was included in the last part of this project for metabolite profiling study.;In Short, this work presents several useful hyphenated techniques of ICP-MS in bioanalysis, proving the tremendous potential of elemental detection in drug development (assisting molecular modification in drug design and metabolite profiling) and therapeutic drug monitoring (hair profiling)

Comments

Principal supervisor: Doctor Leung Kelvin S Y.;Thesis submitted to the Department of Chemistry.;Thesis (Ph.D.)--Hong Kong Baptist University, 2015.;

Bibliography

Includes bibliographical references.

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