No description available.

No description available.

The roam objectives of this PhD project were to relate anal~ te solubility in supercritical carbon dioxide via molecular structure and also to investigate the factors that influence the solubility and extraction of analytes in a supercritical fluid extraction (SFE) when using carbon dioxide as the solvent. The polarity of an analyte was selected as the key parameter to developing a means of estimating steroid solubility in supercritical carbon dioxide. Polarity can be estimated by the hydrophobicity term, log P (based on partition coefficients), and also of the solubility parameter, 0,. The use of partition coefficient in conjunction with a calculated solubility parameter was demonstrated as a reasonable means of estimating steroid solubility in supercritical carbon dioxide. Experimental determination of the solubility of several steroid compounds with a range in polarities in supercritical carbon dioxide was carried out in order to correlate solute polarity to the solute solubility. A chromatographic method was also investigated based on capacity factor measurements for the prediction of steroid solubility in supercritical carbon dioxide. The application of supercritical fluid extraction (SFE) \\<ith carbon dioxide and modified carbon dioxide for the extraction of four antifungals from an animal feed matrix has been investigated. The SFE experiments were designed to optimize e:\.1:raction conditions for the extraction of the antifungals from the animal feed to allow for the evaluation of the most significant variables influencing extraction. A method was also developed for the analysis of the SFE animal feed extracts by packed-column supercritical fluid chromatography. The modification of the mobile phase with polar modifier was necessary to elute the antifungals. The procedure provided an alternative separation selectivity to the existing reversed phase high performance liquid chromatography techniques with much shorter analysis time.

Research has centred on multidimensional chromatographic techniques which utilise the high specificity of immunoaffinity chromatography for extraction of analytes from complex biological matrices. On-line immunoaffinity chromatography-high performance liquid chromatography-mass spectrometry (IAC-HPLC-MS) systems (IAC and HPLC coupled via a loop interface) were developed for the confirmatory analysis of the corticosteroids dexamethasone and flumethasone with MS detection. Utilising an atmospheric pressure chemical ionisation (APCI) LC-MS interface, dexamethasone was confirmed in both spiked and post administration equine urine samples, with a detection limit of 0.1 ug 1-l. Detection by quadrupole ion trap mass spectrometry (ITMS) using a particle beam (PB) interface was performed for dexamethasone and flumethasone in post administration equine urine samples with high precision (6.9-7.4 %) with limits of detection in the range 3-4 ug 1-l. Studies were also conducted in this work into the antibody crossreactivity and non-specific binding of corticosteroids on a HEMA bound anti-dexamethasone lAC column. On-line IAC-HPLC and IAC-HPLC-GC have been developed and assessed for the determination of testosterone in equine urine. A novel approach to interfacing lAC with HPLC being achieved using a porous graphitic carbon (PGC) column. The IAC-HPLC system developed was used for sample pre-treatment for combustion isotope ratio mass spectrometry analysis. The IAC-HPLC and IAC-HPLC-GC systems finally being coupled with mass spectrometry to enable confirmation of the endogenous steroid at 0.5 ug 1-l and 1 ug 1-l respectively in stripped equine urine.

published_or_final_version / Zoology / Master / Master of Science

published_or_final_version / abstract / Obstetrics and Gynaecology / Master / Master of Philosophy

No description available.

No description available.

No description available.

Steroid sulfatase (STS) catalyzes the desulfation of sulfated steroids such as estrone sulfate to the corresponding steroid such as estrone. Inhibitors of STS are believed to have potential for treating estrogen-dependent breast cancer. A new class of potential irreversible suicide inhibitors of STS, based on aryl sulfates bearing a monofluoromethyl or difluoromethyl group ortho to the sulfate group, was synthesized. Key to the success of these syntheses was the use of new sulfation methodology recently developed in the Taylor group. A new and efficient route to 4-formyl estrone, a time-dependent, irreversible STS inhibitor, is also reported. Several new classes of potential, reversible STS inhibitors were synthesized. These compounds are analogs of known STS substrates in which the sulfate group is replaced with an ???,??????-difluoromethylenesulfonamide group, a boronic acid group or a sulfinic acid group. We also report the synthesis of estrone sulfate analogs that bear a carboxylate moiety at the 17-position and a sulfate surrogate at the 3-position. It is anticipated that these compounds will inhibit STS by interacting with Arg98 which lies at the periphery of the active site. Key to the success of this synthesis was the use of the t-butyl group as a protecting group for the 2-position of estrone. Finally, our preliminary investigations into the synthesis of a new class of chiral electrophilic fluorinating agents are presented. These reagents are based on a chiral binaphthyl sulfonimide scaffold and are expected to be capable of performing enantioselective electrophilic fluorinations. Such reagents may be useful in synthesizing organofluorines of biological significance including STS inhibitors.