Synthetic drugs such as piperazines are among the most commonly abused drugs and are typically consumed by younger populations. Because of their popularity, developing optimized analytical strategies designed to improve detection and interpretation of synthetic piperazines is of interest to the forensic community. To improve the likelihood that a substance of interest is detected, careful evaluation into the mass spectrometry signal is required. However, with all analytical pursuits, there is a limit at which the substance cannot be detected with certainty; thus a threshold is commonly referred to as the limit of detection (LOD). Formally, the LOD is the minimum amount of analyte (concentration, mass, number of molecules, etc.) that can be detected at a known confidence level. The purpose of this research was to use common analytical methods to calculate the LOD and verify the results with previous work at the Boston University forensic toxicology laboratory. Data from the Liquid Chromatography-tandem Mass Spectrometer (LC-MS/MS) was previously generated and consisted of signal intensity information in the form of peak height and peak area, from titrations of eight synthetic piperazines that included: Benzylpiperazine (BZP), 1-(3-chlorophenyl)-piperazine (mCPP), 3-trifluoromethylphenylpiperazine monohydrochloride (TFMPP), methylbenzylpiperazine (MBZP), 1-(4-fluorobenzyl)-piperazine (FBZP), 2,3-dichlorophenylpiperazine (DCPP), para-fluorophenylpiperazine (pFPP) and para-methoxyphenylpiperazine (MeOPP). Generally, the LOD is determined by first evaluating the signal in the absence of analyte and determining the probability that signal, , crosses the signal threshold, . The signal threshold is based upon the false detection rate the laboratory can withstand for a given interpretation scheme. In instances where very small levels of false detections can be tolerated, a large is chosen. In other circumstances, where noise detection can adequately be interpreted, a low is chosen. In chromatography and radiography the typical one sided =0.003. The number of molecules for each analyte at each concentration (20 ng/mL, 50 ng/mL, 200 ng/mL, 500 ng/mL, 1000 ng/mL and 2000 ng/mL) was determined and used throughout this work. Peak area signals and ratios versus number of molecules for each analyte were used to, first, visually inspect the linearity of signal to analyte level. It was determined that using internal standards improved linearity, as expected; however, the data suggested that absolute signal intensity was sufficient to compute the LOD for these compounds. Generally accepted methods of calculating LOD were not used for this research as the signal from the blank was not detected most likely due to the sensitivity of the instrument used. This study used an extrapolation of the data and propagation of errors method to calculate the LOD as the signal from the blank was not needed. For all eight analytes, the LOD calculated was similar to the lowest concentration (20 ng/mL) used when validating this method. This research needs to be expanded on to include more concentration points and see the plateau effect at higher concentrations. This will provide information to analytical chemists when a blank signal is not available about how the LOD can be calculated with high confidence.

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

Made available in DSpace on 2016-03-07T19:20:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-09-17. Added 1 bitstream(s) on 2016-03-07T19:24:13Z : No. of bitstreams: 1 000854411_20170917.pdf: 427684 bytes, checksum: 6328427be3c7e3bb317d47f40312ec19 (MD5) Bitstreams deleted on 2017-09-22T12:16:27Z: 000854411_20170917.pdf,. Added 1 bitstream(s) on 2017-09-22T12:17:17Z : No. of bitstreams: 1 000854411.pdf: 2712482 bytes, checksum: 2c6ff9e2456e5f600eb3ac6e153b3a9b (MD5) / Apesar dos recentes avanços em cromatografia líquida monodimensional, a complexidade de algumas amostras exige o emprego de técnicas de separação capazes de oferecer maior poder de resolução e capacidade de picos. Como consequência, o desenvolvimento de técnicas cromatográficas bidimensionais abrangentes (LC×LC, GC×GC, LC×GC) tem recebido atenção crescente nos últimos anos. A principal vantagem dessas técnicas comparadas às técnicas tradicionais é a maior capacidade de picos e possiblidade de se empregar diferentes mecanismos de separação em cada dimensão. O maior desafio relacionado à otimização de métodos desta natureza está relacionado à seleção de complexos parâmetros experimentais, frequentemente baseada na experiência do analista ao invés de rigorosamente estruturada em estratégias teoricamente embasadas. A primeira e mais importante etapa no processo de otimização de métodos LC×LC é a seleção do par cromatográfico (fase estacionária e fase móvel, 1D e 2D). Quando a amostra é precisamente conhecida, algumas características podem servir como um guia qualitativo na seleção destes parâmetros; em outros casos, padrões representativos podem ser empregados para avaliar a correlação entre os sistemas 1D e 2D, porém, quando pouca ou nenhuma informação é disponível, esta continua sendo uma tarefa difícil. Este trabalho apresenta uma nova estratégia de seleção do par cromatográfico empregando amostras reais de extrema complexidade e cálculos de recobrimento da superfície de separação, além da otimização de métodos em cromatografia líquida bidimensional abrangente baseada em planejamentos estatísticos. A amostra selecionada para o desenvolvimento do método foi uma mistura de extratos vegetais previamente estudados pelo grupo de pesquisa, contendo uma vasta diversidade de metabólitos com diferentes características estruturais e... / Despite recent advances in monodimensional liquid chromatography, the complexity of some samples requires the use of separation techniques that can provide greater resolving power and peak capacity. As a consequence, the development of comprehensive two-dimensional chromatographic techniques (LC×LC, GC×GC, LC×LC) has received increasing attention in recent years. The main advantage of these techniques compared to traditional techniques is the largest peak capacity and possibility to employ different separation mechanisms in each dimension. The biggest challenge related to method optimization of this kind of techniques is related to the selection of complex experimental parameters, often based on the analyst's experience rather than theoretically based strategies. The first and most important step in the method optimization process in LC×LC is the selection of the chromatography pair (stationary phase and mobile phase, 1D and 2D). When the sample is precisely known, some features may serve as qualitative guidance in the selection of these parameters; in other cases, representative standards can be used to evaluate the correlation between 1D and 2D systems, however, when little or no information is available, this remains a difficult task. This work presents a new strategy for the selection of the chromatographic pair using real and extremely complex samples and fractional coverage surface calculations, besides the method optimization in comprehensive two-dimensional liquid chromatography based on statistical designs. The sample selected for the method development was a mixture of plant extracts previously studied by the research group and containing a wide diversity of metabolites with distinct structural characteristics and therefore different challenges to be overcome in the chromatographic separation. Employing such strategy and comprehensive elution conditions, it was possible to select the...

Made available in DSpace on 2014-06-11T19:35:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-11-04Bitstream added on 2014-06-13T20:06:28Z : No. of bitstreams: 1 cardoso_jc_dr_araiq.pdf: 1485180 bytes, checksum: 40b02693d9760a4a0c5ab74012ab7413 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Neste trabalho, apresentamos o desenvolvimento de estruturas nanotubulares auto organizadas de dióxido de titânio (TiO2) preparadas pela técnica de oxidação eletroquímica utilizando eletrólito não aquoso na presença de íons fluoreto. Sob condições otimizadas de anodização: 30V por 50 horas nanotubos altamente alinhados, perpendiculares à superfície metálica de titânio metálico, foram produzidas. As caracterizações destas superfícies foram realizadas através das técnicas de microscopia eletrônica de varredura, difração de raio-X e voltametria de varredura linear. Outras estruturas tais como nanofios e nanoporos de TiO2 foram sintetizadas e estes materiais foram utilizados para promover a degradação fotoeletrocatalítica de seis aminas aromáticas. Os resultados obtidos mostram que os nanotubos de TiO2 promovem com grande eficiência na degradação e mineralização de todos os compostos avaliados com quase 100% de rendimento em menos de 3 horas de reação. Ensaios em cromatografia líquida de alta eficiência revelam a formação de subprodutos gerados durante este tratamento, entretanto, todos estes produtos são degradados ao final do processo. Outros poluentes emergentes tais como filtros solares foram submetidos ao mesmo tratamento e as respostas alcançadas revelam uma eficiência no tratamento satisfatória, indicando assim, a versatilidade do sistema de tratamento. A segunda parte deste trabalho consistiu na produção de células solares baseando-se na investigação de heterojunções de nanofios de TiO2 / P3HT (poli(3-hexil tiofeno)) como camadas ativas em dispositivos fotovoltaicos híbridos. Entre estas camadas foi depositada partículas de sulfeto de antimônio (Sb2S3) no propósito de aumentar a fotoeficiência em virtude da absorção na região do visível. Esta deposição foi realizada através... / Here we report the development of self-organized structures of titanium dioxide (TiO2) nanotubes prepared by an electrochemical oxidation technique using non-aqueous electrolyte in the presence of fluoride ions. Under optimized conditions of anodizing, 30V for 50 hours, highly aligned nanotubes perpendicular to the surface of metallic titanium were produced. The surfaces of these were characterized using scanning electron microscopy, X-ray diffraction and linear sweep voltammetry. Other structures such as nanowires and TiO2 nanoparticles were synthesized and these materials were used to promote the photoelectrocatalytic degradation of six aromatic amines. The results show that TiO2 nanotubes very efficiently promote the degradation and mineralization of all compounds evaluated with almost 100% efficiency in less than 3 hours of reaction. Tests on high performance liquid chromatography revealed the formation of by-products generated during this treatment; however, all these products are degraded by the end of the process. Other emerging pollutants such as endocrine disruptors and sunscreens underwent the same treatment and resulted in satisfactory treatment effectiveness, indicating the versatility of the treatment system. The second part of this work was the production of solar cells based on heterojunctions investigation of TiO2 nanowires / P3HT (poly (3-hexyl thiophene)) as active layers in hybrid photovoltaic devices. Between layers were deposited particles of antimony sulfide (Sb2S3) in order to increase photoefficiency due to absorption in the visible region. This deposition was made through the process of chemical bath deposition at low temperatures for a period of 4 hours. Electrodes used were tin oxide doped with fluorine (FTO) and gold (Au). The deposition of TiO2 nanowires was performed using the... (Complete abstract click electronic access below)

Made available in DSpace on 2015-08-20T17:10:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-04-24. Added 1 bitstream(s) on 2015-08-20T17:25:49Z : No. of bitstreams: 1 000840326_20160424.pdf: 113924 bytes, checksum: 3a1cad039c8f76f08b11170e5da617e3 (MD5) Bitstreams deleted on 2016-04-25T15:55:53Z: 000840326_20160424.pdf,. Added 1 bitstream(s) on 2016-04-25T15:56:50Z : No. of bitstreams: 1 000840326.pdf: 1991836 bytes, checksum: 2bc4d69a08c0e41971f42ad21c0a2dcc (MD5) / A cefalotina (CET) é um antimicrobiano β-lactâmico semi-sintético, bactericida e representa o protótipo das cefalosporinas, pertencente à classe da primeira geração. As cefalosporinas apresentam um espectro de atividade mais amplo do que as penicilinas e são amplamente prescritas. Poucos métodos analíticos são descritos na literatura para a análise de CET, e ao nosso conhecimento, nenhum método rápido e indicativo de estabilidade por cromatografia líquida para este composto foi publicado anteriormente. Foi desenvolvido um método indicativo de estabilidade por cromatografia líquida em fase reversa para determinação quantitativa de CET, na presença de impurezas e produtos de degradação gerados a partir dos estudos de degradação forçada em amostras de pó liofilizado para injeção. O método desenvolvido é também aplicável para a determinação de substâncias relacionadas em matéria-prima e em formas farmacêuticas. A separação cromatográfica foi obtida com a coluna Agilent Eclipse XDB-Phenyl, de 250 mm x 4,6 mm, 5 μm, em fase móvel composta por uma mistura das soluções A (tampão fosfato de amônio, pH 4,5) e B (acetonitrila), no modo de eluição gradiente. A vazão utilizada foi de 1,0 mL/min e o comprimento de onda 238 nm. O fármaco foi submetido a condições de estresse por hidrólise, oxidação, fotólise, umidade e degradação térmica. Obteve-se degradação considerável nas condições de hidrólise alcalina, ácida e estresse oxidativo. No método desenvolvido por cromatografia líquida de alta eficiência (CLAE), a resolução entre CET e os seus potenciais produtos de degradação foi maior que 2,4; além disso, a pureza de pico de CET em todas as condições foi maior que 99%, demonstrando o poder indicativo de estabilidade do método. A impureza B (desacetilcefalotina) que é um metabólito menos ativo da CET foi identificada e apresentou formação significativa, especialmente na condição... / Cephalothin (CET) is a semi-synthetic β-lactam antimicrobial compound, bactericidal, and it represents the prototype of cephalosporins, which belongs to the first-generation class. Cephalosporins present a larger spectrum of activity than penicillins and they are widely prescribed. Few analytical methods are described in the literature for the analysis of CET and to our knowledge rapid stability-indicating liquid chromatography (LC) methods for this compound have not been published elsewhere. A stability-indicating gradient reversed phase liquid chromatography (RP-LC) method has been developed for the quantitative determination of CET, in the presence of its impurities and degradation products generated from forced degradation studies, in samples of lyophilized powder for injection. The developed method is also applicable for the related substances determination in bulk drugs and pharmaceutical forms. The chromatographic separation was achieved on an Agilent Eclipse XDB-Phenyl, 250 mm x 4.6 mm, 5 μm column with mobile phase containing a gradient mixture of solutions A (aqueous ammonium phosphate buffer, pH 4.5) and B (acetonitrile) as mobile phase. The flow rate was 1.0 mL/min and the detection wavelength was 238 nm. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis, humidity and thermal degradation. Considerable degradation was found to occur in base, acid and oxidative stress conditions. In the developed high performance liquid chromatography (HPLC) method, the resolution between CET and its potential degradation products was found to be greater than 2.4, further, the peak purity of CET in all conditions were more than 99% proving the stability-indicating power of method. The less active metabolite of CET, desacetylcephalothin (impurity B), was identified and is showed significant formation especially in alkaline condition. This method is able to detect the degradation products of CET at a ...

Orientador: Alberto José Cavalheiro / Co-orientador: Cristiano Soleo de Funari / Banca: Paulo Clairmont Feitosa de Lima Gomes / Banca: Fabíola Manhas Verbi Pereira / Banca: Álvaro José dos Santos Neto / Banca: Carmen Lúcia Cardoso / Resumo: Apesar dos recentes avanços em cromatografia líquida monodimensional, a complexidade de algumas amostras exige o emprego de técnicas de separação capazes de oferecer maior poder de resolução e capacidade de picos. Como consequência, o desenvolvimento de técnicas cromatográficas bidimensionais abrangentes (LC×LC, GC×GC, LC×GC) tem recebido atenção crescente nos últimos anos. A principal vantagem dessas técnicas comparadas às técnicas tradicionais é a maior capacidade de picos e possiblidade de se empregar diferentes mecanismos de separação em cada dimensão. O maior desafio relacionado à otimização de métodos desta natureza está relacionado à seleção de complexos parâmetros experimentais, frequentemente baseada na experiência do analista ao invés de rigorosamente estruturada em estratégias teoricamente embasadas. A primeira e mais importante etapa no processo de otimização de métodos LC×LC é a seleção do par cromatográfico (fase estacionária e fase móvel, 1D e 2D). Quando a amostra é precisamente conhecida, algumas características podem servir como um guia qualitativo na seleção destes parâmetros; em outros casos, padrões "representativos" podem ser empregados para avaliar a correlação entre os sistemas 1D e 2D, porém, quando pouca ou nenhuma informação é disponível, esta continua sendo uma tarefa difícil. Este trabalho apresenta uma nova estratégia de seleção do par cromatográfico empregando amostras reais de extrema complexidade e cálculos de recobrimento da superfície de separação, além da otimização de métodos em cromatografia líquida bidimensional abrangente baseada em planejamentos estatísticos. A amostra selecionada para o desenvolvimento do método foi uma mistura de extratos vegetais previamente estudados pelo grupo de pesquisa, contendo uma vasta diversidade de metabólitos com diferentes características estruturais e... / Abstract: Despite recent advances in monodimensional liquid chromatography, the complexity of some samples requires the use of separation techniques that can provide greater resolving power and peak capacity. As a consequence, the development of comprehensive two-dimensional chromatographic techniques (LC×LC, GC×GC, LC×LC) has received increasing attention in recent years. The main advantage of these techniques compared to traditional techniques is the largest peak capacity and possibility to employ different separation mechanisms in each dimension. The biggest challenge related to method optimization of this kind of techniques is related to the selection of complex experimental parameters, often based on the analyst's experience rather than theoretically based strategies. The first and most important step in the method optimization process in LC×LC is the selection of the chromatography pair (stationary phase and mobile phase, 1D and 2D). When the sample is precisely known, some features may serve as qualitative guidance in the selection of these parameters; in other cases, "representative" standards can be used to evaluate the correlation between 1D and 2D systems, however, when little or no information is available, this remains a difficult task. This work presents a new strategy for the selection of the chromatographic pair using real and extremely complex samples and fractional coverage surface calculations, besides the method optimization in comprehensive two-dimensional liquid chromatography based on statistical designs. The sample selected for the method development was a mixture of plant extracts previously studied by the research group and containing a wide diversity of metabolites with distinct structural characteristics and therefore different challenges to be overcome in the chromatographic separation. Employing such strategy and comprehensive elution conditions, it was possible to select the... / Doutor

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)

Liquid chromatography (LC) in tandem with mass spectrometry (MS) is a measurement tool for obtain information about the compounds in the investigated extracts. There were already developed methods for processing and analysis of measured data sets. However, only partial problems of processing/analysis task were handled independently. Therefore, the rst part describes existing methods and techniques commonly used in the LC-MS for the processing and analysis today. In this thesis an approach based on the theory of systems is used for description of abstract model above the measured data. This model encapsulated all processing/analysis steps into appropriate and consistent mathematical space. The creation of this model via description of the measurement device and data outputs is introduced. Abstract model of LC-MS data set is used to decompose the measurement into three partial contributions, the analyte signal, the random noise and the systemic noise. The separation process of the signal could be estimated using the probabilistic approach. That probabilistic approach to the LC-MS analysis was implemented in the developed software, which was published in the Bioinformatics Journal.