Dissertation presented in partial compliance with the requirements for the Masters Degree in Technology: Chemistry, Durban University of Technology, 2009. / This study was mainly a response to a challenge faced by ESKOM in its coal-fired power stations. In spite of using high purity water to drive the turbines, the latter were damaged by ‘pitting’, possibly related to acids generated at high temperatures. In the light of this a relatively simple method for determination of short chain organic acids was identified by comparing the efficacies of several methods. It was found that high performance liquid chromatography (HPLC) method preceded by derivatization (with o-nitrophenyl hydrazine) is suitable for analyzing mixtures of simple acids at ppb levels. Calibration was effected by using methanoic acid (formic acid), ethanoic acid (acetic acid), propanoic acid (propionic acid) and butanoic acid (butyric acid). The HPLC instrument used was from Thermo Separations with P2000 pump, SN 4000 interface and UV1000 with a column heater. A comparative study between the HPLC methods using ion exclusion and partition chromatography was carried out in order to find a suitable method that can be used with aqueous environmental samples. The two essential columns that were used were ion exclusion Phenomenex Rezex OA column and a Nucleodur C8 column. The method of partition chromatography using a C8 column showed the most success using a mobile phase consisted of acidified water using HCl (pH4.5) along with a 60:40 Acetonitrile/Methanol mixture. Both isocratic and gradient programs were utilized. Limits of detection were improved from 800ppb (formic acid), 480ppb (acetic), 350ppb (propionic) and 680ppb (butyric acid) to 25ppb (acetic), 60ppb (propionic) and 90ppb (butyric). Samples used in analysis were collected from the main stream, economiser, condensers, polishing plant and turbines of the Tutuka Power Station in Mpumalanga province and analysed using with final developed method / Eskom Tertiary Support Programme. Durban University of Technology

Mephenoxalone is a mild central nervous system depressant with activity resembling that of meprobamate. Since its introduction in 1961 mephenoxalone has been used as an anxiolytic and as a muscle relaxant, although the latter effect is weak. Preliminary studies on the absorption and disposition of mephenoxalone have been conducted in beagle dogs but no pharmacokinetic data from human studies have been reported, except for a single study in which the biotransformation products present in human urine were identified. Methods presently available for the determination of mephenoxalone in biological fluids lack the sensitivity, specificity and precision required for detailed pharmacokinetic studies. In this study, a rapid, sensitive, precise reverse-phase high-performance liquid chromatographic method with ultraviolet detection at 200nm was employed for the determination of mephenoxalone in biological fluids. Serum and urine samples were prepared for chromatographic analysis using simple liquid-liquid extraction techniques. The application of the assay to pharmacokinetic studies in humans is presented. After administration of a single oral dose of 400mg mephenoxalone dispersed in 150ml water to six young, healthy volunteers, the compound was rapidly absorbed with the peak concentration of 8μg/ml occurring after about 1 hour. The elimination half-life was approximately 3 hours. The drug was extensively metabolized with only about 1 percent of the administered dose being excreted unchanged in the urine after 24 hours. The bioavailability of a newly developed mephenoxalone-containing tablet was also investigated. The drug was absorbed more rapidly from the tablet than from the dispersed dose. This was attributed to a shorter in vivo dissolution time on the basis of in vitro tests, but this effect is not expected to be clinically significant. In addition, two human urinary metabolites of mephenoxalone were identified as unconjugated hydroxylated derivatives using thermospray HPLC-mass spectrometry. The plasma protein-binding properties of mephenoxalone were also investigated.

Erythromycin, a macrolide antibiotic used mainly against gram-positive bacteria has been in clinical use since 1952 (1). Previous pharmacokinetic data published on this antibiotic have been derived predominantly from microbiological assay techniques. However, these techniques are relatively imprecise as well as being non-specific and extremely tedious to perform. A novel high performance liquid chromatographic analysis of erythromycin in human serum and urine using U.V. detection at 200 nm and/or electrochemical detection using both an amperometric and a coulometric electrochemical detector is presented. The method involves a solid phase extraction procedure followed by a simple phase separation step and chromatography on a reverse phase column. In order to select the optimum U.V. detector for this analysis, five "state of the art" detectors were compared in terms of their signal-to-noise ratios at U.V. wavelengths between 200 and 210 nm. A known metabolite des-N-methylerythromycin is readily detectable using U.V. detection, whilst another metabolite/degradation product anhydroerythromycin is not seen using U.V. detection but is readily observable using an electrochemical detector. The method has a limit of sensitivity of 0.25 μg/mL and 1.00 μg/mL in serum and urine respectively (U.V. detection) and is sufficiently sensitive to monitor serum and urine concentrations of erythromycin in man after administration of a single 500 mg erythromycin stearate tablet. / KMBT_363 / Adobe Acrobat 9.53 Paper Capture Plug-in

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

Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2017. / Crystal engineering involves the manipulation of intermolecular interactions to design functionalised crystalline materials and has proved to be an effective tool for the modification of physicochemical properties of active pharmaceutical ingredients (APIs). In the first section of this study, the aim was to systematically influence the rate of dissolution of a highly soluble active pharmaceutical ingredient using crystal engineering principles. Salicylic acid (SA) was employed as a model API to form multicomponent crystals with a series of selected cinchona alkaloids, namely quinine (QUIN), quinidine (QUID), cinchonine (CINC), cinchonidine (CIND), N-benzylquininium chloride (NBQUIN), N-benzylcinchonidinium chloride (NBCIND) and N-benzylcinchoninium chloride (NBCINC). The resulting novel crystalline forms were found to be salts, and were characterised using single crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. The dissolution profiles of the salicylate salts, measured from an aqueous media using high performance liquid chromatography-mass spectroscopy, show a significant decrease in the rate of dissolution of SA. Subsequently, Hirshfeld surface analysis was used as a tool for quantitative and qualitative comparison of the crystal structures. This study indicates that the rate of dissolution can be successfully influenced by methodically adding extra hydrophobic groups onto the coformer. In the second section, we applied the information obtained from the SA studies to acetylsalicylic acid (aspirin, ASA). We sought to improve its thermal stability and dissolution via the formation of new solid forms with the aforementioned cinchona alkaloids. We successfully synthesized a novel drug-drug salt of an analgesic, non-steroidal antiinflammatory and antipyretic drug (ASA), and an antimalarial and analgesic drug (QUIN). The salt was formed both by using solution methods and liquid assisted grinding - a green chemistry technique. The salt exhibited physicochemical properties different from the parent drugs, and a reduced rate of dissolution. / National Research Foundation(NRF)

Made available in DSpace on 2014-10-09T12:33:45Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:58Z (GMT). No. of bitstreams: 0 / Linfomas são cânceres provenientes da transformação de um linfócito no sistema linfático, sendo que, o mais comum é o Linfoma Não-Hodgkin (LNH). Avanços na imunologia e na biologia molecular têm auxiliado na detecção desses tumores e aberto caminhos para novas estratégias de tratamento, como a Radioimunoterapia. O rituximab é um anticorpo monoclonal quimérico anti-CD20 já utilizado como imunoterápico no tratamento de LNH refratários ou recidivos. O objetivo deste trabalho foi estudar a conjugação deste anticorpo ao quelante bifuncional DOTA-NHS-éster e radiomarcar este imunoconjugado com o radioisótopo 177Lu, com o objetivo de desenvolver um radioimunoterápico para tratamento de LNH. Estudos de imunoconjugação com diferentes razões molares rituximab:DOTA foram estudadas (1:5, 1:10, 1:20, 1:50, 1:250, 1:500 e 1:1000) afim de avaliar qual condição conferia maior pureza radioquímica. A estabilidade dos imuconjugados foi analisada por cromatografia de alta eficiência por até 240 dias em diferentes condições de armazenamento. A estabilidade do imuconjugado radiomarcado foi avaliada após incubação a 2-8 °C e em soro humano a 37 °C e a ligação às proteínas séricas foi determinada. Estudos de biodistribuição foram realizados em camundongos Swiss sadios a fim de caracterizar biologicamente o imunoconjugado radiomarcado. Com o objetivo de analisar se os processos de conjugação e de radiomarcação não danificaram a capacidade de reconhecimento do antígeno (imunorreatividade) deste anticorpo, realizou-se estudos preliminares de ligação às células de LNH (Raji). Os imuconjugados de razão molar baixa (1:5, 1:10 e 1:20) mostraram-se estáveis quando armazenados por até 240 dias em diferentes condições. A análise em cromatografia em camada delgada e CLAE, revelou que o Acm conjugado na razão molar 1:50 foi radiomarcado com alta pureza radioquímica (superior a 95%) quando purificado em coluna PD-10. Este mesmo radioimunoconjugado apresentou razoável estabilidade a 2-8° C. A análise da estabilidade em soro humano não indicou grande metabolismo pelas enzimas do soro. O radioimuconjugado apresentou alta ligação às proteínas séricas indicando clareamento sanguíneo lento, o qual foi confirmado pelos estudos in vivo. O radioimunoconjugado apresentou alta captação no fígado o que é característico de anticorpos monoclonais. Os estudos preliminares de competição indicaram que o processo de obtenção do radioimunoconjugado não prejudicou sua ligação às células Raji sendo esta ligação específica. / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:47:57Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:07:45Z (GMT). No. of bitstreams: 1 08712.pdf: 2365459 bytes, checksum: 3be7f0aa24629302df9709de6db64f86 (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Class of 2012 Abstract / Specific Aims: To assess the chemical stability of ampicillin for injection in normal saline at pH values ranging from 5 to 6. Methods: A stability-indicating high performance liquid chromatography (HPLC) method was developed and used to determine the stability of ampicillin for injection in normal saline following buffering with sodium acetate and acid adjustment with HCl at pH values of 5, 5.5, and 6. To confirm that the assay was stability-indicating, ampicillin trihydrate reference standard (1 mg/mL) was exposed to alkali, acid, and oxidative stress conditions and analyzed by HPLC for the presence of degradation products. Analysis was performed on a reverse-phase (C-18) column with a mobile phase consisting of water, acetonitrile, 1 M monobasic potassium phosphate, and 1 N acetic acid (909:80:10:1). Other HPLC parameters were: flow rate 1 mL/min; detection wavelength 254 nm; injection volume 20 µL; column temperature 30˚C. The method was evaluated for linearity, precision, and accuracy. The chemical stability of ampicillin for injection (18 mg/mL) in normal saline and sodium acetate (pH adjusted at values of 5, 5.5, and 6) was assessed at baseline (t=0), 7, 11, 17, 31, and 44 hours and compared to a control solution (no pH adjustment). Measurements at each time interval were performed in triplicate. Main Results: Ampicillin trihydrate reference standard (1 mg/mL) was adequately separated from degradation products following exposure to alkali, acid, and oxidative stress conditions. After 16 hours, a precipitate was observed in the solution at pH 6, and therefore stability is not reported. All other solutions (pH 5, pH 5.5, and control) were stable for at least 24 hours at room temperature and yielded t90 values of 110, 64.2, and 27.5 hours, respectively. Conclusions: Adjustment of intravenous ampicillin solutions to pH values of 5 or 5.5 significantly increased stability. Ampicillin appears to be most stable at a pH near its isoelectric point (pH 5).

Phenylpropanolamine (PPA), a sympathomimetic amine, has been widely used over the past 40 years as a decongestant and, in much larger dosages, as an appetite suppressant. Considerable interest has recently been shown in this drug due to its increasing popularity as an over-the-counter anorectic agent. Much controversy exists concerning the unfavourable side-effects of PPA resulting from the higher doses required for appetite suppression and the potential of this drug for abuse. A literature search revealed a paucity of information concerning the determination of PPA in biological fluids and, most noticeably, on the pharmacokinetics of this drug. An original method for determining PPA in serum and urine using high performance liquid chromatography (HPLC) which has increased sensitivity over other published HPLC methods is presented here. The simplicity of the extraction from biological fluids and subsequent determination by HPLC, enables concentrations of PPA to be monitored after a single dose of the drug. This method is therefore readily applicable to bioavailability and pharmacokinetic studies. The dissolution profiles of 4 sustained-release formulations of PPA were determined in a modified USP rotating paddle apparatus and the samples analysed using HPLC. A mathematical equation was applied to these data which are expressed in terms of dissolution parameters. Oral test dosage forms and solutions of PPA were investigated in bioavailability trials using the developed HPLC method to analyse the urine and serum samples. Linear one body compartment kinetics were assumed and the WagnerNelson method used to transform in vivo serum data to absorption plots which were then fitted to the well known Weibull equation. In order to more appropriately characterize the kinetic processes of absorption, distribution and elimination, a more complex model was utilized which involved numerical integration of a series of differential equations. The data were fitted to these models using nonlinear regression techniques. The pharmacokinetics of PPA are shown to exhibit some evidence of nonlinearity. The absorption of the drug appears to be di scontinuous and PPA seems to favour a two body compartment model.

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