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Pregnanediol (5B Pregnane- 3⋉- 20⋉- dial) is the chief urinary metabolite of progesterone, and as such is important in that variations in its concentration reflect variations in progesterone secretion. Estimations of pregnanediol concentration are therefore of considerable interest to the obstetrician and gynaecologist. Pregnanediol was first identified in the urine of pregnant women in 1929 by Marrian. Nearly ten years later Venning developed a method by which the glucuronic acid ester of pregnanediol could be extracted from the urine and its concentration gravimetrically determined. Numerous variations of the Venning theme were published in the next few years, each being claimed by its authors to be an improvement on the original. Most of these involved the estimation of the conjugated form, and it was a while before the advantage of estimating the hydrolysed aglycone was realized. Hydrolysis, when it was practised, resolved itself into two methods - namely, hydrolysis by heating the urine with a mineral acid, and enzymic hydrolysis by incubation with beta-glucuronidase. Acid hydrolysis, while producing a less clean hydrolysate, is more rapid and convenient than enzyme hydrolysis, and is used in the Klapper method which is presently the most widely used method in clinical studies. Klapper employs a double chromategraphic column separation of pregnanediol followed by colorimetric evaluation. Variations of Klapper's method have also appeared and not a few investigators have published comparisons of the various methods. Klapper himself compared his method to certain other methods and concluded that his was definitely superior. Of the accuracy of the Klapper method there is no doubt. Subsequent methods have proved more sensitive, but in terms of practicability Klapper's is the method of choice. As was pointed out with some complacency, "practicability is most satisfactory, one technician readily performing some twenty determinations in one week." In contrast to the flood of criticisms, comparisons, variations, claims and counter-claims which accompanied the publication of the abovementioned methods, the thin layer chromatographic method perfected by Waldi attracted very little attention. It is very much more rapid than all other existing techniques, is very sensitive, specific and of acceptable accuracy. In an attempt to ensure its usefulness for clinical and medical research laboratories, the Waldi method has been marketed in 'kit' form. It is intended primarily as a diagnostic aid in establishing pregnancy, and as such it might have enjoyed considerable application had it not been for the advent of the immunological method of pregnancy diagnosis which is very much more rapid. Nevertheless, the Waldi method, used purely as a means of assessing the pregnanediol content of the urine is extremely useful, and it is the purpose of this investigation to establish this usefulness, especially with respect to routine clinical investigations. The validity of some diagnoses which are based on pregnanediol assay results, is also investigated. As it is impossible to explain the significance or usefulness of a pregnanediol assay without first explaining the functions of progesterone, some time and space must be expended in a brief description, firstly, of the role played by progesterone in the phenomenon of the menstrual cycle, and secondly, of its vital importance in pregnancy. It must be realized that progesterone is only one of the many hormones involved in these events, but, in order to limit the introduction of extraneous detail, no mention is made of the other hormonal participants except when necessary for the understanding of the whole. It may be mentioned here that much of the evidence that was used for the elucidation of the functions and origins of progesterone, was derived from studies of its metabolite, pregnanediol.

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The evaluation of the potential to use Ultra Performance Liquid Chromatography (UPLC) for the simultaneous quantification of all the actives in a multi-active tablet is described in this work. Part of the evaluation was to ensure that the necessary regulatory requirements were adhered to by ascertaining that an analytical method is suitable for a specific purpose through analytical method validation for the specific multi-active tablet. The UPLC method was also tested for the analysis of similar products, namely tablet formulations that contain similar active ingredients in the same proportions but with an additional active ingredient. A method for the simultaneous determination of paracetamol, caffeine and codeine phosphate was developed using UPLC technology. The UPLC developed method was more efficient than the existing in-house HPLC method. The UPLC method was then validated in accordance to ICH and USP guidelines. The application of this UPLC method for the analysis of similar products containing paracetamol, caffeine, codeine phosphate and one extra active ingredient was very challenging. The low concentration of the additional component, differences in sample matrix and differences in formulations added to the challenges. The direct application for the analysis of products Y and Z was not successful; however the method could be used as a platform for further research. A cost comparison between the UPLC and HPLC methods showed the UPLC method to be more cost effective. Thus, while maintenance costs are higher for the UPLC instrument, column costs are comparable to HPLC columns, but solvent and waste disposal charges decrease considerably due to lower solvent use. The reduction in instrument time dramatically improves the cost effectiveness of UPLC over HPLC due to a concurrent reduction in analyst time requirement. The results of this study show that the analytical costs associated with the analysis of multi-active drugs using HPLC procedures can be reduced substantially by the CONFIDENTIAL INTELLECTUAL PROPERTY OF ASPEN PHARMACARE implementation of UPLC technology. The hypothesis that the enhanced chromatographic power of UPLC can be leveraged to provide faster analysis times hence increased product throughput rates, and lower operating costs for the analysis of multi-active drugs was accepted. These advantages were achieved whilst meeting all regulatory requirements for analytical methods as required by regulatory bodies.

A method of calculating the RP-HPLC retention indices, based on the alkylarylketone scale, has been developed. The retention indices are calculated from the molecular structure of a compound as the sum of the parent contribution, the parent index, the substituent contributions, the substituent indices, and terms to account for the interactions between substituents, the interaction indices.

In Part I of this work, the decay of O₂(¹Δg) was studied at room temperature in the flow system in the absence of oxygen atoms. The decay of O₂(¹Δg) was classified into first and second order decay with respect to O₂(¹Δg). The rate constant of the main first order decay with respect to O₂(¹Δg), which is considered to be caused by collisions of O₂(¹Δg) with wall of the reaction tube, was found to be 0.25 sec. The total second order decay constant was found to be 2.9 x 10⁴ 1/ mole sec. In Part II the reactions of excited oxygen molecules with some olefins were investigated. 2,3-Dimethyl-3-hydroperoxybutene-1 was identified as the product of the reaction of excited oxygen molecules with 2,3-dimethylbutene-2, 3-Methyl hydroperoxybutene-1 and 2-methyl-3hydro-peroxybutene-1 were produced by the reaction of excited oxygen molecule with 2-methylbutene-2. The decay of O₂(¹Δg) with 2,3-dimethylbutene-2 was also studied but the results could not be explained by any simple mechanism. / Science, Faculty of / Chemistry, Department of / Graduate