List of Titles

Quinolone-Pyrazinamide Derivatives: synthesis, characterisation, in silico ADME analysis and in vitro biological evaluation against Mycobacterium tuberculosis

- Rukweza, Kudakwashe Gerald

Authors: Rukweza, Kudakwashe Gerald
Date: 2023-10-13
Subjects: Quinolone antibacterial agents , Mycobacterium tuberculosis , Antitubercular agents , Tuberculosis Chemotherapy , Drug resistance , Moxifloxacin , Isoniazid
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/390901 , vital:68596
Description: Tuberculosis is one of the leading causes of death worldwide caused by an infectious species, Mycobacterium tuberculosis (Mtb). Some of the factors that contribute to the prevalence of this disease include the complexity of diagnosis, prolonged period of therapy, side effects associated with current TB drugs, the prevalence of resistance against the current treatment options and a high incidence of co-infection with HIV/AIDS. Thus, there is a need for new alternative drugs to provide safer and shorter treatment therapy options that are not susceptible to the development of drug resistance. In this project, we focus our attention on the quinolone pharmacophore. Quinolones are currently used as alternative options in the treatment of resistant strains of Mtb. Previous work pertaining to quinolone-isoniazid hybrid compounds showed promising in vitro activity against the H37Rv strain of Mtb and served as the inspiration to pursue this project. The journey commenced with the synthesis of quinolone-pyrazinamide hybrid compounds (Figure 3.1). These compounds were synthesised, through the attachment of the quinolone and the pyrazinamide entity through a hydrazine linker. The synthesised compounds were purified, and their structural identity confirmed using common spectroscopic techniques including 1H and 13C NMR, infra-red (IR) and mass spectrometry. In vitro biological assays were performed by testing for the activity against the H37RvMA strain of Mtb. The bioassays were performed in triplicates to ensure the accuracy of the results. Moxifloxacin and isoniazid were tested as control compounds. Finally, the resultant compounds were profiled in silico for physicochemical and ADMET properties using open access software SwissADME. All the synthesised compounds 3.8a-f showed no activity against H37RvMA. In most cases, the resulting compounds showed minimal to no activity (MICs ≥ 57.3 μM) in all three media. During the in vitro studies, the compounds showed significant precipitation in the media over time suggesting poor aqueous solubility. The SwissADME analysis of these compounds indicated poor solubility in aqueous media, which is likely linked to their molecular size and complexity. Despite poor aqueous solubility, compounds 3.8a-f showed acceptable physicochemical properties and ADME parameters. No PAINs (Pan-assay interference compounds) were observed. Minimal to no interaction with CYP enzymes were predicted. Most of the compounds were compatible with the Lipinski’s rules of five. , Thesis (MSc) -- Faculty of Science, Pharmacy, 2023
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Date Issued: 2023-10-13

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High-performance liquid chromatographic studies of the acid degradation, pharmacokinetics and comparative bioavailability of erythromycin

- Glew, Fiona

Authors: Glew, Fiona
Date: 1989
Subjects: High performance liquid chromatography , Erythromycin -- Analysis , Erythromycin -- Pharmacokinetics , Erythromycin -- Bioavailability
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3737 , http://hdl.handle.net/10962/d1001529
Description: Erythromycin is a macrolide antibiotic with a spectrum similar to penicillin and is used mainly in the treatment of infections caused by gram-positive organisms. Since its discovery in 1952, erythromycin has achieved wide-spread clinical use. Susceptibility of erythromycin base to inactivation by acid results in decreased availability following exposure to acidic gastric fluids. Formulation of acid resistant dosage forms and the preparation of acid stable chemical derivatives have been attempted to improve absorption and subsequent clinical efficacy . Two of the most commonly used erythromycin derivatives are the stearic acid salt (erythromycin stearate) and the lauryl sulphate salt of the propionyl ester (erythromycin estolate). Although it has been known for many years that erythromycin is susceptible to acid degradation, very few reports on the stability of erythromycin in aqueous solutions appear in the literature. In this study, a high-performance liquid chromatographic system using electrochemical detection was employed for a kinetic study of erythromycin degradation. The effect of varying acid pH on the degradation rate of both erythromycin base and erythromycin stearate, and the effect on the hydrolysis rate of erythromycin estolate is presented. In addition, the effect of temperature on erythromycin degradation was also investigated. Until recently, the majority of pharmacokinetic and bioavailability studies have utilized relatively non-specific microbiological assay procedures. However, in this study a solid phase extraction, followed by the use of a high-performance liquid chromatographic system using electrochemical coulometric detection was employed for the determination of erythromycin in biological fluids. Human volunteers each received enteric coated erythromycin base pellets in capsule dosage form and also film coated erythromycin stearate tablets on separate occasions. Results from the clinical trials revealed the enteric coated erythromycin base pellets had a greater bioavailability than the film coated erythromycin stearate tablets. Computer fitting of data revealed no intra-volunteer variability in elimination rate constants, suggesting differences in serum levels following administration of both dosage forms are due to variation in absorption. Results from the clinical trials were also compared with those obtained from a further trial, during which the same volunteers received erythromycin estolate
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Date Issued: 1989

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Phenylpropanolamine : analytical and pharmacokinetic studies using high-performance liquid chromatography

- Scherzinger, Sabine Hilda

Authors: Scherzinger, Sabine Hilda
Date: 1988
Subjects: Phenylpropanolamine , Pharmacokinetics , High performance liquid chromatography
Language: English
Type: text , Thesis , Masters , MSc
Identifier: vital:3811 , http://hdl.handle.net/10962/d1004528
Description: Phenylpropanolamine (PPA), a synthetic sympathomimetic amine structurally related to ephedrine has been widely used over t he past 40 years as a nasal decongestant and appetite suppressant. It has been the focus of much controversy concerning the efficacy of the drug in its use as an anorectic agent, and due to the side effects caused by the higher doses of PPA required for appetite suppression. Although extensively used, there is little information concerning the determination of PPA in biological fluids and on the pharmacokinetics of this drug. An adaptation of a published high-performance liquid chromatographic (HPLC) assay for PPA in serum and urine using U.V. detection at 210 nm is presented. PPA was separated in the reversed phase mode. The method has a limit of sensitivity of 5.0 ng/mL and 10.0 ng/mL in serum and urine respectively. Serum concentration data following a single 25 mg dose of phenylpropanolamine in human volunteers demonstrate the application of the analytical method for bioavailability and pharmacokinetic studies. After the administration of 25 mg, 50 mg or 100 mg PPA.HCl solutions to 5 human volunteers, a dose proportionality study demonstrated that PPA appears to exhibit linear kinetics. Linear one body compartment kinetics were assumed and the wagner-Nelson method used to transform in vivo serum data to absorption plots. The serum data were fitted to a model using nonlinear regression techniques to characterize the pharmacokinetic processes of PPA. The absorption of phenylpropanolamine appears to be discontinuous and the drug seems to favour a two body compartment model. The pharmacokinetic parameters obtained from a steady state study using multiple dosing of PPA.HCl solutions compared with those found from previous studies after the administration of sustained-release formulations. A plasma protein binding study using equilibrium dialysis demonstrated that PPA is not highly protein bound in the blood.
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Date Issued: 1988

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The influence of sex steroids on pineal enzymes

- Daya, Santylal

Authors: Daya, Santylal
Date: 1982 , 2013-03-28
Subjects: Steroid hormones , Pineal gland , Testosterone , Progesterone
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3808 , http://hdl.handle.net/10962/d1003720 , Steroid hormones , Pineal gland , Testosterone , Progesterone
Description: The influence of the gonadal sex steroids namely, estradiol, progesterone and testosterone on the two major enzymes responsible for the synthesis of melatonin in the pineal gland was investigated. These enzymes are Serotonin-N-acetyltransferase (SNAT) and Hydroxyindole-O-methyltransferase (Hl0MT). Testosterone was found to be the only sex steroid capable of influencing SNAT activity whereas all three of the sex steroids were found to influence Hl0MT activity in a biphasic dose-dependent manner. The influence of these sex steroids on radiolabeled serotonin metabolism by pineals in organ culture was also investigated. Ovariectomy, castration and the sex steroids were all found to alter the pattern of the radiolabeled serotonin metabolism by these pineal glands in organ culture. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
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Date Issued: 1982

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Development of a high pressure liquid chromatographic method for the simultaneous analysis of sulphamethoxazole and trimethoprim and its application to biological fluids and dissolution rate studies on solid oral dosage forms

- Gochin, Rosa

Authors: Gochin, Rosa
Date: 1980
Subjects: High performance liquid chromatography , Body fluids -- Analysis , Drugs -- Dosage forms
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3735 , http://hdl.handle.net/10962/d1001524
Description: Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
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Date Issued: 1980

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Phytochemical studies on certain South African species of the rutaceous genera Agathosma Willd. and Zanthoxylum L

- Finkelstein, Nathan

Authors: Finkelstein, Nathan
Date: 1979
Subjects: Zanthoxylum Rutaceae
Language: English
Type: Thesis , Doctoral , PhD
Identifier: vital:3725 , http://hdl.handle.net/10962/d1001460
Description: Selected species of two South African rutaceous genera, Agathosma Willd. and Zanthoxylum L., were phytochemically studied. Two species of the former genus, A. puberula (Steud.) Fourc . and A. elavisepala R. A. Dyer, yielded a novel O-prenylcoumarin, puberul in, the structure of which was fully elucidated as 6,8- dimethoxy-7-prenyloxycoumarin. This represents the first report of a coumarin from that endemic genus. In another study the alkaloids in three species of Zanthoxylum, Z. davyi (Verdoorn) Waterm., Z. thorneroftii (Verdoorn) Waterm. and Z. humile (E .A. Bruce) Waterm . , were investigated. Chelerythrine, nitidine, (-) -α-N-methylcanadine, (+)-laurifoline and (+)-magnoflorine were isolated and characterized in the stem and root bark of Z. davyi, while the root bark of Z. thorneroftii contained skimmianine and decarine in addition to the alkaloids present in Z. davyi. Skimmianine, decarine, N-norchelerythrine, chelerythrine, (-)-α-N-methylcanadinc, candicine and tembetarine were identified in the root bark of Z. humile. The chemotaxonomic significance of these alkaloids occurring in the South African taxa in relation to other African Zanthoxylum taxa, is discussed. Several non-alkaloids (lupeol, β-sitosterol and (-)-sesamin) were also isolated and characterized in Z. davyi and Z. humile. Horizontal cellulose column chromatography and low pressure liquid chromatography have been applied to the separation of quaternary alkaloids
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Date Issued: 1979

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An investigation into the effect of particulate solids on certain antimicrobial preservatives in pharmaceutical and cosmetic suspensions

- Horn, Norman Robert

Authors: Horn, Norman Robert
Date: 1978
Subjects: Drugs -- Preservation , Drugs -- Microbiology , Cosmetics -- Preservation , Cosmetics -- Microbiology
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3848 , http://hdl.handle.net/10962/d1012436 , Drugs -- Preservation , Drugs -- Microbiology , Cosmetics -- Preservation , Cosmetics -- Microbiology
Description: Pharmaceutical and cosmetic preparations must be formulated so as to assure elegance of appearance, efficacy of ingredients and a satisfactory shelf life as the product. If the formulation is not self-preserving and if it contains material which could act as a substrate for growth of micro-organisms, the shelf life aspect involves, in addition to several other factors, the choice of a suitable antimicrobial preservative. Such preservatives, when present in the minimum effective concentration, are unfortunately prone to interact with many other materials. A number of papers on the inactivation of preservatives by containers, filters and formulation components have been published. The field has been adequately reviewed by de Navarre (1962), Wedderburn (1964) and, more recently, by Coates (1973). From these reviews and from a study of the literature it became apparent that relatively little work had been done on interactions between preservatives and solid particles in aqueous suspension. Consequently, a range of preservatives not previously investigated in this respect was tested for loss of activity in the presence of fifteen powders commonly used in aqueous suspension in pharmaceutical and cosmetic formulations. In view of the information obtained in this preliminary study and after the development of more satisfactory analytical techniques it was decided to study in greater depth the interaction between these powders and selected organomercurials and quaternary ammonium compounds.
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Date Issued: 1978

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Secondary effects of oral contraceptives

- Yuen, E Ho

Authors: Yuen, E Ho
Date: 1978
Subjects: Oral contraceptives , Oral contraceptives -- Side effects
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3847 , http://hdl.handle.net/10962/d1012296
Description: Norethynodrel, a common progestin in oral contraceptives, produces in female rats several significant physiological, cytological and biochemical changes at dose levels of 1 mg and 20 mg per kg: 1) a relative increase in liver mass 2) modification of appearance and extent of the endoplasmic reticulum 3) augmentation of the protein content of the liver 4) increase of the level of cytochrome P- 450 in the liver as determined by : a) difference spectroscopy b) increases in biotransformation of aniline and aminopyrine in vitro and c) reduction of sleeping times of rats dosed with phenobarbital The significance of these findings becomes evident when it is realized that norethynodrel affects and is affected by the same enzyme system which oxidizes medicaments in general in the body: induction of cytochrome P-450 by administration of norethynodrel may interfere with the action of other drugs . Ethinyl estradiol alone showed none of the inductive effects. At high dose levels (20 mg per kg) both norethynodrel and ethinyl estradiol caused a marked inhibition of growth of the animals, producing a net loss of body mass over the 30- day experimental period. Electron micrographic evidence implies that there is also a lowering of glycogen content and a chemical change in the lipids of adrenocortical and liver cells accompanying the use of these agents.
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Date Issued: 1978

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Studies on the metabolism of SKF 525 A|

- Barber, Peter John

Authors: Barber, Peter John
Date: 1978 , 2013-10-14
Subjects: Drugs -- Metabolism , Cytochrome P-450
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3835 , http://hdl.handle.net/10962/d1007591 , Drugs -- Metabolism , Cytochrome P-450
Description: Spectrophotometric studies have been carried out to determine the pH dependence of binding of SKF 525 A, Brietal sodium and carbon monoxide to cytochrome P-450. The optimal pH for metabolic conversion of SKF 525 A has been investigated and this agent and its major metabolite, SKF 8742 A, have been metabolised in vitro by swine and rat hepatic microsomes. A suitable gas liquid chromatography assay has been developed and used to analyse metabolic production. The effects of carbon monoxide, dithiothreitol, n-octylamine and of induction of cytochrome P-450 by phenobarbital on metabolism of SKF 525 A and SKF 8742 A have been investigated. Attempts have been made to synthesise SKF 525 AN-oxide. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
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Date Issued: 1978

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The effects of organic perturbants on the structure of soluble collagen

- Hart, Geoffrey Joseph

Authors: Hart, Geoffrey Joseph
Date: 1971
Subjects: Chemistry, Organic , Collagen
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3846 , http://hdl.handle.net/10962/d1012157 , Chemistry, Organic , Collagen
Description: Organic solvents were used in the present study as a means of investigating the non-covalent interactions involved in the maintenance and pertubation of the three-dimensional structure of the collagen macromolecule in solution. The two main types of non-covalent interaction under consideration are hydrogen bond formation and hydrophobic effects. Elucidation of the relative importance of these factors in the maintenance of the solution structure of proteins is an area of intensive investigation and fundamental significance to biochemistry as a whole. During the past decade, considerable progress has been made towards a clearer understanding of the forces involved, and a number of different theoretical and experimental approaches have emerged. Until about 1960, hydrogen bonding was widely believed to be the dominant non-covalent interaction responsible for the maintenance of secondary and tertiary structure in many proteins. Subsequently, an increasingly important role for apolar (hydrophobic) effects was suggested by a number of authors, and at present there is no satisfactorily definitive interpretation of the available experimental evidence. The current work is based on a comparison of the effects of organic solvents on widely different substrates, namely collagen, cellulose, and the chromatographic reference material, catechin. The chromatographic mobility of catechin on cellulose may be regarded as a phenomenon which is mediated entirely by polar interaction mechanisms. The effects of various organic perturbants and of changing solvent/water ratios are readily interpreted on this basis. In the collagenous systems, however, certain results appear to require the introduction of concepts other than those relating exclusively to polar bonding affinities. The experimental evidence shows that there are cases where the enhancement of the polar interaction potential of solvent/water mixtures, in relation to catechin-cellulose systems, is accompanied by an apparent reduction of polar interaction potential of the same solvent/water mixtures with respect to soluble collagen. The anomaly outlined above will be discussed in terms of two fundamentally different theoretical assumptions. In the first of these, the mechanism of perturbant action in collagenous systems is regarded as essentially similar to that governing catechin-cellulose affinity patterns. Thus, interaction processes are all treated as polar phenomena, in which direct hydrophobic destabilization of the collagen triple helix plays no part. In an attempt to explain the effects of perturbants in both collagen and cellulose-containing systems in terms of the above assumption, two hypotheses are examined involving (1) direct polar interaction between perturbant molecules and functional groups of the protein; (2.) the possibility of an enhanced polar interaction potential of water molecules, due to lowering of the environmental dielectric constant when organic solvents are added to the systems. Within the other broad conceptual division, collagen and cellulose substrates are considered to respond in fundamentally different ways to the action of organic perturbants. As before, cellulose-catechin-solvent interactions are treated as entirely polar phenomena, and perturbant effects interpreted in terms of mechanisms such as direct solvation of the substrate, and the enhanced hydrogen bonding activity of water molecules. In contrast, perturbant lyotropic action with respect to soluble collagen i s viewed as the manifestation of a major contribution by hydrophobic interaction processes to macromolecular stability. Thus, solvents that competitively reduce the assumed entropic contribution to the stability of the collagen triple helix, are seen as potential destabilizers of the native state of the protein and inhibitors of the regeneration of co-operative structures during renaturation. Both of the above approaches are critically assessed in the light of the present work and the dominant trends apparent in the recent literature.
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Date Issued: 1971

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An investigation into the loss of preservatives from opthalmic solutions, during filtration sterilization

- Naidoo, Nadasen T

Authors: Naidoo, Nadasen T
Date: 1970
Subjects: Filters and filtration , Sterilization
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3851 , http://hdl.handle.net/10962/d1012931
Description: Most eye drops are dispensed in multi-dose containers, hence protection should be given against microbial contamination during use. To remain sterile during it's use, the solution should contain a preservative in such concentration so that it kills micro-organisms in a short time. It has been stated in the literature that the instillation of contaminated eye drops constitutes a greater danger than the intravenous injection of a contaminated solution since the cornea is nonvascular and lacks the normal antimicrobial defences of the blood stream. Amongst the preservatives used, those included in the official formulations for eye drops are Chlorhexidine Acetate, Phenyl Mercuric Nitrate, Benzalkonium Chloride, and to some extent Phenylethanol, which may be used in combination with Benzalkonium Chloride. The main purpose of this investigation has been to determine the adsorption of these preservatives by different filters during sterilization by filtration. Part 1, p. 2.
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Date Issued: 1970

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An investigation of compounds occurring in leonotis species

- Naidu, Krishna

Authors: Naidu, Krishna
Date: 1970
Subjects: Leonotis -- Analysis , Chemistry -- Analytic , Nuclear magnetic resonance
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3852 , http://hdl.handle.net/10962/d1012934
Description: Two labdane diterpenoids 8-hydroxymarrubiin and leonitin were isolated from Leonotis dysophylla (Benth.) and Leonotis leonitis respectively. Spectral studies of 8-hydroxymarrubiin, C₂₀H₂₈ O₅ʻ showed the presence of a β -substituted furan, a Ϫ-lactone, three tertiary methyl groups and tertiary hydroxyl group (s). The NMR spectrum of 8-hydroxymarrubiin and marrubiin C₂₀H₂₈O₄ʻ were almost identical with the exception of the C₁₇- methyl group which appeared as a singlet in 8-hydroxymarrubiin and as a doublet in marrubiin. The extra oxygen atom was therefore assumed to be present as a hydroxyl group substituted in the C₈₋ position. This was further confirmed by the formation of an epoxide and a Ϫό-dilactone. Leonitin, C₂₀H₂₈O₇ʻ was shown by spectral and chemical evidence to be a diterpenoid dilactone possessing an ester function and an ether linkage. Comparison of the NMR spectra of compound X and leonitin suggested that the acetoxy function occurs in the C₂₀- position. This was further supported by the formation of a 'Ϫό -dilactone. The absence of a β -furan moiety was apparent from chemical and spectral evidence, A structure for leonitin is proposed and aspects of its stereochemistry discussed.
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Date Issued: 1970

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An investigation into some aspects of the thin layer chromatographic assay of Pregnanediol with emphasis on the suitability of this method as a clinical laboratory routine

- Paton, L T

Authors: Paton, L T
Date: 1969
Subjects: Thin layer chromatography , Pregnanediol
Language: English
Type: Thesis , Masters , MSc
Identifier: vital:3853 , http://hdl.handle.net/10962/d1013023
Description: 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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Date Issued: 1969

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