Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.447974
Title: Applications of gas chromatography and mass spectrometry to steroids and other biologically important materials
Author: Anthony, Geoffrey M.
ISNI:       0000 0001 3425 1869
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1973
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Abstract:
General Techniques have been developed for the structural analysis of microgram quantities of some biological materials using gas chromatography end mass spectrometry. The work has been mostly limited to two types of material (i) beta-hydroxy-amines and related catecholamines (ii) natural and synthetic steroids The latter type, the study of which constitutes most of this thesis, presents special difficulties due to the many positions on the steroid nucleus which may contain a functional group. The substituent groups studied are alkyl, olefin. hydroxyl and carbonyl. Methods are developed for obtaining structural information directly (where the course of fragmentation under electron impact is not known) and by methods which require a knowledge of ion fragmentation processes. Considerable use is made of derivatives for hydroxyl and carbonyl modification to improve gas chromatographic properties, and to assist in functional group characterisation. Such assistance is afforded by:- (a) molecular weight increment giving the number of functional groups capable of forming the derivative, and (b) the ability of the derivative to direct mass spectral fragmentation to produce ions characteristic of the group's location. PART 1: beta-HYDROXY-AMINES AND CATECHOLAMINES A study is made of the usefulness of alkyl and aryl boronic acids as derivatives of beta-hydroxy-amines and related catecholamines. This bifunctional reagent reacts with both the catechol and hydroxy-amine groups. Both of these types of derivatives are amenable to gas chromatographic study, and from the mass spectra it is possible to identify the groups R' and R". PART 2 - ALKYLAED STEROIDS A study is made of alkylated and nor-steroids as their trimethylsilyl ethers. The location of methyl groups on steroids of the testosterone type is shown to be possible by means of gas chromatographic retention increments and by shifts in m/e values of ione in the mass spectrum. PART 3 - OLEFINIC STEROIDS One of the more exacting problems inherent in steroid analysis is the locations of some olefinic groups by mass spectrometry. Although olefinic bonds may modify the fragmentation of neighbouring groups, the mass spectra of steroids often give no direct indication of the location of isolated unsaturation. A study is made of isomeric Delta4, Delta5(10) and Delta5 estren-17-ones which give almost identical mass spectra. Chemical modification, such as oxidation of the olefin with osmium tetroxide and derivatisation of the resulting cis-diol, is shown to assist in characterising these three isomers by gas chromatography and mass spectrometry. PART 4 - OXYGENATED STEROIDS AND TERPENOIDS A technique of depreciation by gas liquid chromatography is developed and applied to the examination of some steroids and terpenoids. Saturated and unsaturated ketonen are shown to give satisfactory exchange of enolic hydrogen with deuterium after gas chromatography on basic columns saturated with deuterium oxide. Subsequent mass spectrometry shows the extent of deutoriation which is informative for location of the carbonyl group, Ethynyl groups (which are present in some progestational steroid drugs) and hydroxyl groups are also shown to exchange acetylenic or hydroxylic hydrogen with deuterium after deuteriation. The use of trimethylsilyl ethers and O-methyl- oximes as derivatives for "blocking" exchange at hydroxylic and enolic positions is demonstrated, thereby permitting selective deuteriation at unprotected groups. PART 5- STEROID DRUG METABOLISM Some of the above techniques are applied to the study of urinary metabolites of the anabolic steroid drug "Nilevar" (17alpha-ethylestr-4-en-17beta-ol-3-one) enabling tentative structures to be postulated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.447974  DOI: Not available
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