Thesis (PhD.(Chemistry)--University of Pretoria, 2008. / On title page: Submitted in partial fulfilment of the requirements for the degree Doctor of Philosophy in Chemistry in the faculty of Natural and Agricultural Sciences of the University of Pretoria. Includes bibliographical references.

Asthma, current detection methods and metabolites proposed as asthma markers are described. The limitation of the disease diagnosis is outlined and metabolomics is introduced as the approach carried out within this research with the potential to measure the group metabolites that characterise the metabolic responses of a biological system to a specific disease. Chemistry underlying breathing, current breath collection and analytical techniques are described as well as detection and data processing technology associated within our research. A work-flow for the collection, analysis and processing of exhaled breath samples in respiratory diseases is described. The non-invasive sampling method allows collection of exhaled breath samples on children and adults without experiencing any discomfort. The analysis of exhaled breath samples using thermal desorption gas chromatography mass spectrometry outlines the use of retention index for the alignment of VOCs retention time shifting over time. This methodology enables the creation of a breath matrix for multivariate analysis data processing where each VOC is defined by retention index and most intense fragments of the mass spectrum. This methodology is tested in two cohorts of participants: paediatric asthma and severe asthmatic participants whose breath profiles are compared against healthy controls and within the two asthmatic phenotypes to prospect the markers that differentiate between the different groups. Eight candidate markers are identified to discriminate between asthmatic children and healthy children and seven markers between asthmatics undergoing therapy and healthy controls. The database from severe and paediatric asthma is compared, establishing seven non-age related markers between the two groups. A new interface is developed for the faster analysis of exhaled breath samples using thermal desorption ion mobility mass spectrometry. The interface front end has been modified and optimised to achieve the best sensitivity and resolution of VOCs in exhaled breath. A preliminary study carried out in a small cohort of volunteers shows the feasibility of the technique for the differentiation of asthmatic and healthy adults.

A wide range of organic compounds are released from building and furnishing products and these have the potential to adversely affect indoor air quality. There are growing international requirements for testing and controlling these emissions for the protection of public health. The test methods require specialist analytical chemistry facilities based on thermal desorption/gas chromatography/mass spectrometry (TD/GC/MS). This project has addressed the need for better performance and greater automation of the analysis, as well as development of simpler screening tests. A variety of products were tested using screening techniques, with an emission cell method being used as a reference test. Short duration tests, using a micro-scale chamber at slightly elevated temperature, were shown to have the potential to predict emissions occurring during longer term reference tests. Multi-sorbent air sampling tubes, that have the potential to extend the volatility range of compounds determined by a single TD/GC/MS analysis, were compared with Tenax TA tubes specified by current standard methods. This showed no difference in performance for the range of compounds for which Tenax is optimal, with improved performance for a number of more volatile compounds. The determination of formaldehyde was investigated using 2-hydroxymethylpiperidine as a derivatising agent, followed by TD/GC/MS. The results showed the possibility of this method being developed as an alternative to the current standard method that involves solvent elution and liquid chromatography. The performance of a newly developed time-of-flight mass spectrometer was compared with a standard quadrupole instrument. This showed its potential, with the use of re-collection, to extend the concentration range of compounds quantified from a single air sample, of particular benefit for the determination of carcinogens. New compound identification software was applied to increase automation of analysis of the TD/GC/MS data. Good correlation with manual processing was achieved, demonstrating the possibility of routine application to material emissions testing.

Etylenglykol (EG) är ett toxiskt ämne som kan orsaka livsfarliga komplikationer. Syftet med studien var att genom systematiska litteratursökningar göra en sammanställning och en jämförelse av metoder som används för direkt kvantifiering av EG i patientprov. Studien utfördes med en systematisk litteraturstudiemetod, genom litteratursökning i två databaser: PubMed och MEDLINE. Datasökningens resultat var 12 vetenskapliga artiklar som validerade fyra direkta kvantifieringsmetoder. De kvantifieringsmetoderna av EG delades upp i fyra grupper: enzymatiska, gaskromatografi med flammajoniserings detektor (GC-FID), gaskromatografi masspektrometri (GC-MS) och vätskekromatografi-tandem-masspektrometri (LC–MS-MS). De fyra metoderna jämfördes för att bestämma vilken metod som har bäst sensitivitet och specificitet. Däremot kunde denna jämförelse inte utföras i GC-MS och LC–MS-MS på grund av avsaknad data för vissa sensitivitet och specificitet parametrar och därav så jämfördes endast enzymatisk metoder och GC-FID mot varandra. Slutsatsen av jämförelsen mellan GC-FID och enzymatiska metoder har antytt på att den termiska desorption-gaskromatografi med flammajoniserings detektor (TDC-GC-FID), som var en ny utveckling av GC-FID, var den bästa metoden utifrån dens sensitivitet och specificitet. Det behövs dock utföras studier där alla fyra metoder testas för samma parametrar för att bestämma den absoluta bästa metoden för direkt kvantifiering av EG. / Ethylene glycol (EG) is a toxic substance that can cause life threatening complications. The aim of this study was through systematic literature searches create a summary and comparison between methods used for direct quantification of EG in patient samples. The study performed a literature study in the databases: PubMed and MEDLINE. The data search resulted in 12 scientific articles that validated four direct quantification methods.  Those methods were: enzymatic, gas chromatography with flame ionizing detector (GC-FID), gas chromatography mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS-MS). The four methods were compared to decide which method had the best specificity and sensitivity. This comparison could not be done in GC-MS and LC-MS-MS due to missing data for certain specificity and sensitivity parameters and therefore only GC-FID and enzymatic methods were compared to each other. The conclusion of the comparison between GC-FID and enzymatic methods have resulted in that the thermal desorption gas chromatography with flame ionizing detector (TDC-GC-FID), that was a newly developed GC-FID, was the best method due to its specificity and sensitivity. Future studies where all four methods are tested for the same parameters to decide the absolute best method for direct quantification of EG is needed.

Transport phenomenon of gas and vapors through polymer barrier materials as well as the factors affecting permeability of gaseous and liquid toxic compounds were investigated and results are presented in this thesis. Permeation characteristics investigation methods were elaborated and verified with focusing on utilization of gas chromatographic method and its instrumental modifications.