Orientador: Hérida Regina Nunes Salgado / Banca: Taís Maria Bauab / Banca: Cristiane Masseto de Gaitani / Resumo: O enrofloxacino é uma fluorquinolona de segunda geração derivada do ácido nalidíxico, desenvolvida na década de 1980, sendo a primeira fluorquinolona introduzida na medicina veterinária para o tratamento de várias infecções bacterianas. Existem vários trabalhos na literatura que descrevem métodos analíticos para análise de enrofloxacino em formas farmacêuticas, porém poucos para comprimidos. A maior parte deles envolve a cromatografia líquida de alta eficiência (CLAE) com fases móveis constituídas por soluções-tampão, as quais podem danificar o sistema cromatográfico, ou métodos que envolvem o gasto de grandes quantidades de solventes orgânicos. Desta forma, este trabalho teve como objetivo principal o desenvolvimento, validação e otimização de métodos analíticos para análise de enrofloxacino na forma farmacêutica de comprimidos, que apresentem menor impacto sobre o meio ambiente e que sejam mais práticos, mais seguros para os operadores e mais econômicos do que as metodologias analíticas descritas para o enrofloxacino. O enrofloxacino foi analisado qualitativamente quanto à umidade, solubilidade e faixa de fusão. Também foi realizada análise por espectrofotometria no infravermelho e desenvolvido método por cromatografia em camada delgada (CCD) indicativo de estabilidade. Quanto à análise quantitativa, foi validado método por CLAE com detecção DAD a 278 nm, fase móvel composta por solução aquosa de ácido acético 5% e metanol (75:25, v/v) e faixa de concentração de 6,0 a 14,0 μg/mL, exatidão de 100,14%, teor de 100,94% e tempo de retenção médio de 5,1 minutos; ensaio microbiológico pelo método turbidimétrico, na faixa de concentração de 4,0 a 8,0 μg/mL, utilizando Staphylococcus epidermidis ATCC 12228, com exatidão de 100,01% e potência de 97,84%; e espectroscopia na região do infravermelho, na faixa de concentração de 1,0 a 3,0 mg/150 mg, exatidão de 98,00% e teor de 99,74%. ... / Abstract: Enrofloxacin, a second generation fluoroquinolone derivative of nalidixic acid, developed in the 80's, was the first fluoroquinolone introduced in veterinary medicine for the treatment of various bacterial infections. There are several published studies in literature that describe analytical methods for enrofloxacin in pharmaceutical dosage forms, but a few for tablets. Most of them are related to high performance liquid chromatography (HPLC) using mobile phases constituted by buffer solutions, which may damage the chromatographic columns over time, or methods that involve, mostly, the use of large amounts of organic solvents. In this way, this study aimed to develop new analytical methods for the analysis of enrofloxacin in tablets, which have the lowest impact on the environment as possible and that be more convenient, safer for operators and more economical than the analytical methodologies already described for enrofloxacin. Enrofloxacin was analyzed qualitatively in relation to moisture content, solubility and melting range. Furthermore, it was performed an analysis by infrared spectroscopy and was developed a stability indicative method by thin layer chromatography (TLC). Regarding the quantitative analysis, it was validated HPLC methodology with PDA detection at 278 nm, mobile phase composed by aqueous 5% acetic acid and methanol (75:25 v/v), the concentration range from 6.0 to 14.0 μg/mL, accuracy of 100.14%, content of 100.94% and average retention time of 5.1 minutes; microbiological assay by turbidimetric method, in the concentration range from 4.0 to 8.0 μg/mL, using Staphylococcus epidermidis ATCC 12228, with average accuracy of 100.01% and 97.84% of content; and infrared spectroscopy, in the concentration range from 1.0 to 3.0 mg/150 mg, 98.00% of accuracy and content of 99.74%. Validation of the methods was conducted according to ICH guidelines and Brazilian legislation. The developed methods showed no statistical ... / Mestre

O objetivo desse estudo foi comparar o desempenho de ligaduras ortodônticas estéticas de 4 marcas comerciais, após 30 dias na cavidade bucal, com o uso de dentifrício clareador e convencional para avaliar: alteração de cor por meio da espectrofotometria; a ultraestrutura da superfície por meio da Microscopia Eletrônica de Varredura (MEV); propriedade elástica por meio do teste de tração. Foram avaliadas as ligaduras seguintes marcas comerciais: American Orthodontics, 3M Unitek, Orthotechnology e Morelli Ortodontia. Foram selecionados, após o cálculo amostral, 20 pacientes que atenderam aos critérios de inclusão. Os pacientes receberam, de forma aleatória, com o auxílio do acessório Shooter (TP Orthodontics, La Porte, IN, EUA) ligaduras nos elementos 13, 23, 33 e 43; 32, 31, 41 e 42. No mesmo dia receberam dentifrício clareador Colgate Luminous White (Colgate-Palmolive Indústria e Comércio, São Bernardo do Campo, SP, Brasil) que foi usado por 30 dias (grupo experimental). Após esse período as ligaduras foram removidas, armazenadas (em saliva artificial) e, imediatamente submetidas aos testes. Os pacientes receberam, então, dentifrício convencional Colgate Máxima Proteção Anti-cáries (Colgate-Palmolive Indústria e Comércio, São Bernardo do Campo, SP, Brasil) (grupo controle). Após 30 dias, foram removidas, armazenadas e submetidas aos ensaios. As ligaduras inseridas nos bráquetes dos caninos foram avaliadas para alteração de cor pelo espectrofotômetro (Vita Easyshade Zahnfabrik, Bad Säckingen, Alemanha). Em seguida, as ligaduras, de cada marca, que apresentaram maior e menor variação de cor com o dentifrício clareador e convencional, bem como ligaduras novas, foram submetidas à avaliação qualitativa com a visualização pelo Microscópio Eletrônico de Varredura (EVO 50, Carl Zeiss, Cambridge, Inglaterra). As ligaduras que estavam inseridas nos bráquetes incisivos inferiores foram submetidas ao teste de tração pela Máquina de Ensaio Mecânico Universal (EMIC DL 2000, São José dos Pinhais, PR, Brasil). Os achados foram submetidos à análise estatística ANOVA e ao teste complementar de Duncan em um nível de significância de 5%. Os resultados mostraram que o dentifrício clareador não conseguiu efetivamente manter a estabilidade de cor das ligaduras ortodônticas estéticas. O valor final para o ΔE (variação total de cor) para todas as marcas foi > 3,3 o que indica uma alteração clinicamente perceptível pelo olho humano e que sinaliza a reposição do material por razões estéticas. Em relação à MEV as imagens obtidas foram heterogêneas e não permitiram caracterizar um padrão para um ou outro dentifrício. No que se refere ao teste de tração, houve melhor desempenho para as marcas 3M Unitek e American Orthodontics. O tipo de dentifrício, clareador ou convencional, não alterou a propriedade elástica entre as marcas estudadas. Pode-se concluir, pela presente pesquisa, que o dentifrício clareador não foi capaz de alterar a estabilidade de cor nas 4 marcas avaliadas por um período de 30 dias. A avaliação qualitativa pela MEV não permitiu concluir se a abrasividade do dentifrício clareador trouxe danos ou injurias à superfície das ligaduras. Apesar disso, o seu uso não alterou a propriedade elástica das mesmas. / The objective of this study was to compare the performance of aesthetic orthodontic ligatures/modules of 4 commercial brands, after 30 days in the oral cavity, with the use of conventional and whitening dentifrice to evaluate: color change by spectrophotometry; the ultrastructure of the surface by Scanning Electron Microscopy (SEM); elastic property by the tensile test. The following brands were evaluated: American Orthodontics, 3M Unitek, Orthotechnology and Morelli Orthodontics. Twenty patients who were included in the inclusion criteria were selected after sample calculation. Patients received, at random, with the aid of the Shooter accessory (TP Orthodontics, La Porte, IN, USA) ligatures on elements 13, 23, 33, 43, 32, 31, 41 e 42 and whitening dentifrice Colgate Luminous White (Colgate-Palmolive Indústria e Comércio, São Bernardo do Campo, SP, Brazil), which was used for 30 days (test group). After this period, the ligatures were removed, stored (in artificial saliva) and immediately submitted to the tests. Patients were then given conventional toothpaste Colgate Maximum Anti-caries Protection (Colgate-Palmolive Indústria e Comércio, São Bernardo do Campo, SP, Brazil). This was the control group. Once again, after 30 days, the modules were removed, stored and submitted to assays. Ligatures inserted into the canine brackets were evaluated by the spectrophotometer (Vita Easyshade Zahnfabrik, Bad Säckingen, Germany) to evaluate the color change. After this step, the ligatures of each brand, which presented greater and lesser color variation, both with the whitening dentifrice as well as the conventional one, and new ligatures, were selected for qualitative evaluation with the visualization by the Scanning Electron Microscope (EVO 50, Carl Zeiss, Cambridge, England). The ligatures that were inserted in the lower incisor brackets were subjected to the tensile test by the Universal Mechanical Testing Machine (EMIC DL 2000, São José dos Pinhais, PR, Brazil). The findings were submitted to ANOVA statistical analysis and Duncan\'s complementary test at a significance level of 5%. The results showed that the whitening dentifrice failed to effectively improve the color stability of aesthetic orthodontic ligatures. The final value for ΔE (total color change) for all brands was > 3.3 which indicates a change clinically perceptible by the human eye and signaling the replacement of the material for aesthetic reasons. In relation to the SEM the images obtained were heterogeneous and did not allow to characterize a standard for one or the other dentifrice. Regarding the tensile test, there was better performance for the brands 3M Unitek and American Orthodontics. The type of dentifrice, whitening or conventional did not alter the elastic property between the brands studied. It can be concluded from the present research that the whitening dentifrice was not able to change the color stability in the 4 brands evaluated for a period of 30 days. The qualitative evaluation by SEM did not allow the conclusion that the abrasiveness of the whitening dentifrice caused damage to the surface of the ligatures. Despite this, their use did not alter their elastic property.

Routine pipette calibration is an essential part of any quality assurance and quality control program in the forensic sciences and beyond. Pipette calibration standards in a forensic laboratory are typically set to the limits outlined by the document ISO8655, published by the International Organization for Standardization for the general scientific community. Alternative methods exist that may be capable of monitoring pipette stability across time in a forensic setting. Statistical process control charts, or Shewhart charts, are one such form of process control, which is being investigated for its potential application to pipette calibration monitoring for forensic DNA laboratories. Indeed, the application of process control lines for monitoring the calibration of volumetric equipment is not without precedent.1 To investigate the applicability of process control charts for monitoring pipette stability, a series of X ̅ and S charts, a type of Shewhart chart, have been produced from eight years of collected calibration data. A total of 71 pipettes of the following sizes were examined: 1-10 µL, 1-10 µL multi-channel, 10-100 µL, 100-1000 µL, 1-3 µL, 30-300 µL, 5-50 µL, 5-50 µL multi-channel, and 500-5000 µL pipettes. The ISO8655 calibration recommended volume limits of these pipettes have been added to the charts for the purposes of comparison. With these charts, it is possible to assess pipette performance over time in comparison to the ISO8655 calibration standards and to the control limits imposed by the Shewhart charts. The completed charts suggest that the methodology proposed by Shewhart shows promise as a supplement to ISO8655 recommendations for monitoring pipette stability across time. To corroborate the value of using Shewhart charts to monitor pipette performance, a serial dilution study in conjunction with a series of simulations with dynamic modeling software was performed. This dilution study investigated whether the systematic biases shown by the Shewhart charts could be measured in a laboratory setting. The simulations investigated multiple hypothetical pipetting scenarios concerning various levels of systematic bias. The simulations consistently corroborated the value of Shewhart charts to enforce better compliance between a pipette’s nominal and actual volume delivery, while the serial dilution study offered partial evidence of systematic pipetting bias.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Tereza Morávková Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of Thesis: Assessment of the complex stoichiometry of the active dexrazoxane metabolite ADR-925 with iron and copper by the standard Job'smethod Iron and copper are important trace elements which participate on many physiological processes in humans. Their kinetics in the organism is tightly regulated since both lack or excess of these elements are associated with pathological states. Free ions of iron and copper can catalyse reactive oxygen species (ROS) production and hence cause damage to proteins and DNA. Imbalance in these metals is linked with diabetes, cardiotoxicity, cirrhosis of the liver and neurodegenerative diseases as Alzheimer's disease or Parkinson's disease. Dexrazoxane is a drug with documented protecting effect against cardiotoxicity of anthracyclines. A former theory associated its protective effects against these cytotoxic drugs with the iron-chelating properties of its active metabolite ADR-925. The goal of this diploma thesis was to explore if ADR-925 is able to chelate Fe2+ , Fe3+ , Cu+ a Cu2+ ions at physiologically and pathophysiologically relevant pH values (4,5; 5,5; 6,8 and 7,5) and...

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Performed at: University of defence in Brno, Faculty of Military Health Sciences in Hradec Králové, Department of Toxicology and Military Pharmacology Student: Michaela Mackurová Leader of diploma thesis: PharmDr. Marie Vopršalová, CSc. Supervisor: kpt. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Evaluation of the efficacy of quarternary acetylcholinesterase reactivators in vivo NPL belongs to compounds of organic phosphorus and they are very common cause of poisoning as organophosphorus nerve agent. They can be absorbed by various routes - inhalated, ingest or by transdermal penetration. The problem is ineffective therapy and there is still no broad-spectrum reactivator able to efficiently restore AChE activity after intoxication by various organophosphates that will penetrates into CNS. The main aim of this experiment was to determine and compare the reactivating efficacy of two newly developed oximes K869 and K870 with commonly used oximes K160 and HI-6 against intoxication of sarin. The activity of reactivation was determined by standard spectrophotometric Ellman's method with using male Wistar laboraty rats. The results were evaluated as percentage of reactivation...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Lucia Hanuščinová Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmDr., PhD. Title of diploma thesis: Ability of copper chelators to interact with iron and zinc Copper plays in the human organism a role of an element with indispensable significance, whose biological influence and effects depend on its quantity. With elevated concentrations in the human body, copper becomes toxic, resulting in pathological conditions. The most well-known diseases is the Wilson's disease, whose treatment consists of oral administration of chelators, i.e. chemical compounds, which are capable of binding copper ions in various proportions and eliminating them from the organism. Chelation therapy is currently the first choice after confirmation of the diagnosis. Chelation toxicity results from several factors, e.g. inhibition of copper dependent enzymes or low selectivity to metals. And precisely the selectivity of chelators is being discussed in this diploma thesis. An ideal chelator should not interact with any of the other physiological ions, that are necessary for the proper functioning of the organism. Five of the most frequently therapeutically or experimentally used substances /trientine, D-penicillamine,...

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this study was evaluate the performance of two spectrophotometer devices in assessing color changes of dental enamel after artificial caries induction (demineralization) and treatment with fluorides. The Easyshade spectrophotometer (VITA, Germany) and SP60 (Ex-Rite, USA) were used to measure the color changes of 30 bovine enamel blocks (n=10) in evaluation times: initial (sound enamel) (T0), demineralized enamel (T1 after pH cycling) and after treatment with fluoride agents 5 applications of fluoride gel (2% sodium fluoride group NaF and 1.23% acidulated phosphate fluoride APF group) (T2 to T6). The specimes in control group were kept in deionized water during the experimental time and received no treatment with fluoride. Obtained color change values (ΔE) as well as the values of each CIE L*a*b* dimensions were subjected to ANOVA and Tukey s post hoc test (α=0,05). The Pearson s correlation coefficient was used to measure a correlation study between the two devices. Results showed tha SP60 device was able on identifying and monitoring enamel color changes (p=0.000) and CIE L*a*b* dimension on evaluation times (p=0.000). On other hand, Easyshade showed no significant differences in main factors evaluation time (p=0.713) and treatment (p=0.684). Low correlation between the two devices was observed (r=0.25; p= 0. 001). Based on the obtained results, one can conclude that spectrophotometer SP60 was able to identify enamel color changes during enamel de-remineralization. Color changes in enamel were not assessed by Easyshade device. / O objetivo do trabalho foi avaliar o desempenho de dois espectrofotômetros, na mensuração das alterações do esmalte dentário submetido a desmineralização e tratamento com fluoretos. Os espectrofotômetros Easyshade (VITA, Alemanha) SP60 (Ex- Rite, EUA) foram utilizados para mensurar as alterações ópticas de 30 blocos de esmalte bovino (n=10) nos momentos de avaliação inicial (esmalte hígido) (T0), esmalte desmineralizado (T1 após ciclagem de pH) e durante o tratamento das lesões de mancha branca com agentes fluoretados 5 aplicações tópicas de gel fluoretado ( fluoreto de sódio a 2% - grupo NaF e flúor fosfato acidulado 1,23% - grupo FFA) (T2 à T6). Os espécimes pertencentes ao grupo controle foram mantidos em água deionizada durante o período experimental e não receberam tratamento com fluoretos. Os dados obtidos referentes à alteração de cor (ΔE) bem como das dimensões CIE L*a*b* foram submetidos a analise de variância e teste de contraste de Tukey (α=0,05). O coeficiente de correlação de Pearson foi utilizado para medir a possível correlação entre os dois aparelhos do estudo. Os resultados do trabalho apontaram que o aparelho SP60 foi capaz de identificar e monitorar as diferenças de alteração de cor (ΔE) do esmalte nos diferentes momentos de avaliação (p= 0.000), assim como, foi capaz de informar variações em cada um dos parâmetros CIE L*a*b* (p=0.000). Por outro lado, o aparelho Easyshade, não apontou diferenças significantes entre os momentos de avaliação (p=0.713) e entre os grupos experimentais (p=0.684). Baixa correlação entre os dois dispositivos foi observada (r=0,25; p= 0,001). Com base nos resultados obtidos, foi concluído que o espectrofotômetro SP60 foi capaz de identificar essas alterações nos diferentes tempos de avaliação. No entanto, o aparelho Easyshade não foi capaz de avaliar alterações ópticas no esmalte, decorrentes da perda de minerais e do tratamento com agentes fluoretados.

Aliskiren is the first representative of a new class of drugs, the low molecular weight renin inhibitors, orally active and clinically used in a new effective treatment for hypertension. In the present study, the methods were developed and validaded for assessment of aliskiren in pharmaceutical products. Aliskiren samples were also submitted to the physicochemical tests, meeting the specifications. The analysis by reversed-phase liquid chromatography were performed using Waters XBridge (150 mm x 4.6 mm i. d.), maintained at 25 °C. The mobile phase was consisted of acetonitrile/ water (95:5, v/v)/ 25 mM phosphoric acid pH 3.0 (40:60, v/v), run at flow rate of 1 mL/min and using UV detection at 229 nm. The chromatographic separation was obtained within 3.68 minutes. The spectrophotometric method was also developed and validaded, and the aliskiren can be quantified at 279 nm, using water as diluent. The procedures were validated evaluating parameters such as the specificity, linearity, precision, accuracy, limits of detection and quantitation, and robustness, giving results within the acceptable range. The proposed methods were applied for the analysis of pharmaceutical products, showing significant correlation (P > 0.05) of the results. The dissolution test was developed using 900 mL of 0.1 M of chloridric acid 37 ± 0.5 °C as dissolution medium, apparatus paddle at a stirring rate of 50 rpm and quantitation by spectrophotometric method. Therefore, the procedures can be applied to improve the quality control of pharmaceutical products and to assure the safety and therapeutic efficacy of the drug. / O alisquireno é o primeiro representante de uma nova classe de inibidores da renina, de baixo peso molecular e ativo por via oral, sendo utilizado clinicamente em um novo e eficaz tratamento para a hipertensão arterial (HA). No presente trabalho, foram desenvolvidos e validados métodos para avaliação de alisquireno em produtos farmacêuticos. Submeteram-se os produtos aos testes físico-químicos, mostrando que cumprem as especificações. As análises por cromatografia líquida em fase reversa foram realizadas utilizando coluna Waters XBridge (150 mm x 4,6 mm d. i.), mantida à 25 ºC. A fase móvel foi composta de acetonitrila/ água (95:5, v/v)/ ácido fosfórico 25 mM pH 3,0 (40:60, v/v), eluída na vazão de 1 mL/min e detecção no ultravioleta a 229 nm. A separação cromatográfica foi obtida no tempo de 3,68 minutos. Paralelamente, desenvolveu-se e validou-se método por espectrofotometria no ultravioleta (UV) em 279 nm, utilizando água como diluente. Os procedimentos foram validados, avaliando-se os parâmetros de especificidade, linearidade, precisão, exatidão, robustez e limite de detecção e quantificação, cujos resultados cumpriram os requisitos preconizados. Os métodos propostos foram aplicados na análise de produtos farmacêuticos, demonstrando correlação significativa dos resultados (P > 0,05). Desenvolveu-se método de dissolução do fármaco, utilizando como meio 900 mL de ácido clorídrico 0,1 M mantido a 37 ± 0,5 °C, aparato pá, rotação de 50 rpm e quantificação por espectrofotometria no UV. Desse modo, estabeleceram-se procedimentos que podem ser aplicados para aprimorar o controle da qualidade de medicamentos, bem como contribuir para garantir a segurança e eficácia no uso terapêutico.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this study was to evaluate the color of composite resins when stored in water and red wine, during different periods (immediately after polymerization, 24 hours, 30 days and 180 days) comparing the two measurements of spectrophotometers (Easyshade - Vita and SP60 - X-Rite). Four resin composites were used in two opacities (dentin and enamel): Filtek Supreme XT, Ice, and Opallis Brilliant. After confection 14 specimens (sp) for each resin composite using a metal matrix with 10 mm diameter and 2 mm thick, light cure with a LED (±800mW/cm2) by 40s, sp were polished with Sof-Lex Pop On and felt disc with diamond paste, washed with water and dried with gauze. Immediately after polishing, the initial measurement of the sp was performed, using the CIE L * a * b *. The sp of each composite resin were divided into two groups (n = 7) according to the storage media. Successive readings were taken at 24h, 30 days and 180 days. The color change (ΔE) was calculated using the formula ΔE = ((ΔL)2 + (Δa)2 + (Δb)2)½. The data were subjected to Student t Test and Pearson Linear Correlation for comparison of two spectrophotometers, and ANOVA and Tukey (5%) for each spectrophotometer. In both spectrophotometers, the resins immersed in red wine showed greater change than those kept in water and these values increased over time for most resins. For ΔE obtained by the SP60, the sp immersed in water remained stable, contrary to what was measured by Easyshade that had color changes over time. Although the values of ΔE measured at Easyshade and SP60 were significantly different, they were highly correlated. / O objetivo deste trabalho foi avaliar a cor de resinas compostas quando armazenadas em água e em vinho tinto, durante períodos distintos (imediatamente após a fotoativação, 24h, 30 dias e 180 dias) comparando a leitura realizada por dois espectrofotômetros (Easyshade - Vita e SP60 - X-Rite). Foram utilizadas 4 resinas compostas em 2 opacidades (esmalte e dentina): Filtek Supreme XT, Ice, Brilliant e Opallis. Após a confecção de 14 corpos-de-prova (cps) para cada resina composta, utilizando uma matriz metálica com 10 mm de diâmetro e 2 mm de espessura, fotoativados com um LED (±800mW/cm2), por 40s, os cps foram polidos com discos Sof-Lex Pop On e disco de feltro com pasta diamantada, lavados em água e secos com gaze. Imediatamente após o polimento, foi feita a mensuração inicial dos cps nos dois aparelhos utilizando o sistema CIE L* a* b*. Os cps de cada resina composta foram divididos em dois grupos (n=7) de acordo com os meios de armazenamento. Sucessivas leituras foram realizadas nos períodos de 24h, 30 dias e 180 dias. A alteração de cor (ΔE) foi calculada utilizando a formula ΔE = ((ΔL)2 + (Δa)2 + (Δb)2)½. Os dados foram submetidos ao Teste t de Student e Correlação Linear de Pearson para comparação dos dois aparelhos e à Análise de Variância e Teste de Tukey (5%) para cada um dos aparelhos. Nos dois aparelhos, as resinas imersas em vinho tinto apresentaram maior alteração que as mantidas em água e esses valores aumentaram ao longo do tempo para a maioria das resinas. Para ΔE obtidos pelo SP60, os cps mantidos em água mantiveram-se estáveis, ao contrário do que foi mesurado pelo Easyshade que teve alterações de cor com o passar do tempo. Embora os valores de ΔE mensurados pelo Easyshade e SP60 tenham sido significativamente diferentes, eles foram altamente correlacionados.

Made available in DSpace on 2014-06-11T19:25:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-02Bitstream added on 2014-06-13T20:33:02Z : No. of bitstreams: 1 cazedey_ecl_me_arafcf.pdf: 802368 bytes, checksum: 7af4d6526e6d1c491bb231f706185aea (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O cloridrato de ciprofloxacino, um antibacteriano quinolônico, apresenta amplo espectro de ação e é eficaz in vitro contra praticamente todos os patógenos Gram-negativos, incluindo Pseudomonas aeruginosa. Mostra-se também eficaz contra microrganismos Gram-positivos, como estafilococos e estreptococos. A importância de desenvolver e validar métodos analíticos para este fármaco é justificada por seu potencial terapêutico, grande emprego em terapias microbianas e baixo custo, assim como pelo conhecimento de que a baixa qualidade dos produtos anti-infecciosos está relacionada ao desenvolvimento de cepas resistentes, como consequência da administração de doses subterapêuticas. Por tal razão, é de enorme importância o desenvolvimento de métodos analíticos eficazes e confiáveis para o controle de qualidade dos medicamentos comercializados. Neste trabalho foram desenvolvidos métodos de análise para o cloridrato de ciprofloxacino em solução oftálmica. Os métodos desenvolvidos e validados foram: (i) doseamento microbiológico, método turbidimétrico na faixa de concentração de 14,0 a 56,0 μg/mL, utilizando Staphylococcus epidermidis ATCC 12228 IAL 2150, com exatidão de 99,71% e teor de 102,27%; (ii) método espectrofotométrico na região do UV a 275 nm com faixa de concentração de 2,0 a 7,0 μg/mL, utilizando água como solvente, com exatidão de 101,51% e teor de 99,79%; (iii) método espectrofotométrico derivativo na região do visível a 386,4 nm, na primeira derivada, com faixa de concentração de 50,0 a 100,0 μg/mL, utilizando cloreto férrico 1,0% como reagente, com exatidão de 99,83% e teor de 106,72%; (iv) método por cromatografia líquida de alta eficiência com detector UV a 275 nm, com fase móvel composta por ácido acético 2,5% v/v, metanol e acetonitrila (70:15:15, v/v/v) e faixa de concentração de 1,0 a 6,0 μg/mL, exatidão... / Ciprofloxacin hydrochloride, a quinolone antibiotic, presents a wider spectrum of activity and is effective against practically all Gram-negative pathogens, including Pseudomonas aeruginosa. It is potent against Grampositive microorganisms, as Staphylococcus and Streptococcus. Analytical methods for quantitative determination of ciprofloxacin hydrochloride is important due to its therapeutic potential, wide use in antimicrobial therapy and low cost. Moreover, it is known that the poor quality antibiotic product is direct related development of resistant strains, as consequence of subtherapeutic doses administration. Thus, it is important to develop efficient analytical methods for quality control commercialized products. In this work, analytical methods for determination of ciprofloxacin hydrochloride were validated: (i) microbiological assay, turbidimetric method at concentration range 14.0 to 56.0 μg/mL, using Staphylococcus epidermidis ATCC 12228 IAL 2150 as indicator microorganism, accuracy 99.71% and quantitation of 102.27; (ii) UV spectrophotometry at 275 nm with concentration range of 2.0 to 7.0 μg/mL, using water as solvent, with accuracy of 101.51% and quantitation of 99.79%; (iii) Derivative visible spectrophotometric method at 386.4 nm, in first derivate, with concentration range of 50.0 a 100.0 μg/mL, using 1.0% ferric chloride as reagent, with accuracy of 99.83% and quantitation of 106.72%; (iv) HPLC method with UV detector at 275 nm using 2.5 M acetic acid (v/v), methanol and acetonitrile (70: 15: 15, v/v/v) as mobile phase and concentration range of 1.0 to 6.0 μg/mL, accuracy of 100.11%, quantitation 103.25% and mean retention time of 2.6 minutes; (v) Indirect titrimetric method using bromate/bromide solution in acid medium as reagent in concentration range of 1.0 to 11.0 mg/mL, with accuracy of 100.28% and quantitation of 98.97%.