Analytical studies of trace quantities of oxygenated sterols by GC-MS

• Main Author: Dickson, Sandra R.
• Published: Glasgow Caledonian University 2013
• Subjects: 616.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636798

Coronary heart disease caused by atherosclerosis is a major cause of premature deaths in developed countries . The etiology of atherosclerosis is unknown although elevated serum cholesterol levels are implicated as a major risk factor, and lipid lowering drugs have been successful in its treatment. Oxygenated sterols have also been implicated4 although due to their diversity, trace amounts compared to cholesterol and cholesterol autoxidation producing altifacts less is known of their risk. The work in this thesis optimised extraction and instrumental parameters that led to improved detection of oxysterols in serum. This was done through extraction and emichment of the oxysterols which removed the higher levels of 'swamping' cholesterol. Then by using novel derivatives and the softer negative ion chemical ionisation, this allowed the current to be concentrated in the molecular ion thus improving sensitivity. The determination of non-artifact cholesterol oxides which were prepared by adding perchloric acid to the serum, allowed for the assumption that subsequent cholesterol oxides formed in the work-up must be autoxidation artifacts. This allowed for a more accurate method of quantifying oxysterols in serum. The perchloric acid catalysed rearrangement of cholesterol oxides produced Cholestanetriol and Westphalin's diol which have been characterized with respect to standard compounds. However the elucidation of the structure of the third product, another ene diol was accomplished here using NMR and GC-MS studies since no standard reference compound was available. Trace oxysterols were identified and quantified in serum, through the optimization of parameters which improved detection and by the determination of autoxidation products.