Date of Award

2012

Document Type

Doctoral Thesis

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Dr. Ambrose Furey

Abstract

Serotonin is a major neurotransmitter in the brain and affects various functions both in the brain and in the rest of the body. It has been linked to depression, migraines, and aggression, as well as many psychiatric disorders including schizophrenia, dementia and anorexia nervosa. It also has been associated with conditions like Alzheimer’s disease along with other neurotransmitters such as dopamine.

The aim of this research project is to develop various mass spectrometric methods for the analysis of serotonin, dopamine and similar indoles in both urine and serum matrices. This thesis provides extensive reviews detailing a general overview of serotonin and related compounds, an introduction to mass spectrometry theory and the instruments used in the experimental section of this work, as well as an extensive review on the topic of ion suppression in mass spectrometry. Ion suppression is an important area of method development when dealing with complex samples such as biological matrices and can often be overlooked in tb early stages of method optimisation.

This thesis presents a fully validated LC-MS/MS method and sample preparation methods for the analysis of serotonin, hydroxyindole acetic acid and dopamine in urine and serum. An extensive study into the effect of ion suppression from the various matrices was also carried out for this method. The fourth chapter details a preliminary clinical study investigating the use of serotonin, dopamine or hydroxyindole acetic acid as a biomarker for the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) in children aged between 6-18 years. The fifth chapter presents a LC-MS/MS method for serotonin, dopamine and melatonin in serum using HybridSPE-Precipitation cartridges for sample clean-up.

The final two chapters present two high mass accuracy methods using a LTQ Orbitrap mass spectrometer. These methods use different techniques for sample introduction, one being a liquid chromatographic method for separation of analytes and the other being a direct infusion method using nano-electrospray. The methods provide a novel approach to the analysis of serotonin md related compounds.

Access Level

info:eu-repo/semantics/openAccess

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