This thesis describes bioanalytical methods for drug determination in biological matrixes, with drugs in focus used against diseases largely affecting low-income countries. Solid-phase extraction is used for sample cleanup, and processed samples are analyzed by liquid chromatography. Developed bioanalytical methods are validated according to international guidelines. Eflornithine (DFMO) is a chiral drug, used for treating human African trypanosomiasis. A bioanalytical method for determination of DFMO enantiomers in plasma is presented. The enantiomers are detected by evaporative light-scattering detection. The method has been applied to determination of D-DFMO and L-DFMO in rats, after intravenous and oral administration of racemic DFMO. It is concluded that DFMO exhibits enantioselective absorption, with the more potent enantiomer L-DFMO being less favored. Sulfadoxine (SD) and sulfamethoxazole (SM) are sulfa-drugs used for malaria and pneumonia respectively. Two methods are described for simultaneous determination of SD and SM in capillary blood sampled on filter paper. The former method allows direct injection of extracts from dried blood spots (DBS), while for the latter method solid-phase extraction is added. Pre-analytical factors contributing to measurement uncertainty is also discussed, and it is concluded that it is of high importance that homogeneity in type of sampling paper and sampling volume is assured. Piperaquine (PQ) is an antimalarial, increasingly used in artemisinin combination therapy. A method for determination of piperaquine in DBS is presented. By using a monolithic LC column, a very short LC analysis of two minutes per sample is achieved. A method for simultaneous determination of three antiretroviral drugs i.e. lamivudine (3TC), zidovudine (AZT) and nevirapine (NVP), in DBS samples is described. The method is applied to drug determination in two subjects after receiving standard antiretroviral treatment. Conclusion is that the method is suitable for determination of 3TC and NVP, and to some extent for AZT.

Made available in DSpace on 2017-07-10T18:08:20Z (GMT). No. of bitstreams: 1 Andreine Aline Roos.pdf: 2960540 bytes, checksum: 99bd1c80529add7a7c94dc586e17b240 (MD5) Previous issue date: 2013-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Environmental contamination is a serious problem in today's society and for years aroused the interest of researchers. The pollutants with pharmacological activity are worrying the scientific community by increasing detection of these aquatic environments at concentrations ranging from µ L-1 to ng L-1, which are resistant to conventional treatments used in sewage treatment plants. Thus, it becomes necessary to investigate more effective treatments to minimize environmental contamination. The Advanced Oxidation Processes have attracted interest as promising treatments for removal of organic pollutants, among which stands out the heterogeneous photocatalysis whose the main drawback is the difficulty of separating the catalyst from solution degraded. To try to solve the problem, this work proposes the use of cellulose acetate/TiO2 composite and zinc metal plate coated with ZnO as catalysts for photodegradation of sulfamethoxazole. The composite was prepared by phase inversion of a solution of cellulose acetate and titanium tert-butyl orthotitanate that resulted in a composite with around 4% (in mass %) if TiO2.This composite proved not to be efficient in the degradation of sulfametoxazol in the presence of hydrogen peroxide under both, sunlight or artificial radiation. For this reason the continuity of the work occurred only with zinc plate coated with ZnO obtained by hydrothermal method. The 22 factorial experimental design, with triplicate on central point showed that the model was valid, and that the process was favored with increasing amounts of H2O2 at acidic pH. The equilibrium time for the photodegradation of sulfametoxazol using a plate Zn/ZnO was 120 minutes with removal of 95%, under artificial radiation, obeying the rate law of peudo-first order. The COD and nitrate concentration indicated that there was a small mineralization of the pollutant, despite the high removal, showing that there was probably the formation of intermediate species. Furthermore, the Zn/ZnO showed a catalytic efficiency almost unchanged up to 10 repetitions of photodegradation. However, at the end of the process the zinc concentration in the sample was above the allowed degraded by environmental agencies, necessitating the use of a post-treatment for removal of zinc or use of sulfametoxazol solution with pH closer to neutrality to avoid dissolution of the metal catalyst. / A contaminação ambiental é um grave problema da sociedade atual e há anos desperta o interesse dos pesquisadores. Os poluentes com atividade farmacológica vêm preocupando a comunidade científica pela crescente detecção dos mesmos em ambientes aquáticos, em concentrações que variam de µg L-1 a ng L-1, os quais são resistentes aos tratamentos convencionais empregados nas estações de tratamento de esgoto. Dessa forma, torna-se necessário a investigação de tratamentos mais eficientes para minimizar a contaminação ambiental. Os Processos Oxidativos Avançados vêm despertando interesse como tratamentos promissores para remoção de poluentes orgânicos, dentre os quais destaca-se a fotocatálise heterogênea, cujo principal empecilho é a dificuldade de separação do catalisador da solução degradada. Para tentar solucionar o problema, o trabalho propõe a utilização de catalisadores diferenciados como, compósito acetato de celulose/TiO2 e uma placa de zinco metálico recoberto com ZnO para a fotodegradação do princípio ativo sulfametoxazol. Contudo, o compósito acetato de celulose/ TiO2 não apresentou a eficiência similar ao TiO2 como era esperado, e assim optou-se por prosseguir os estudos de fotocatálise heterogênea utilizando a placa de zinco recoberta com ZnO como catalisador. O planejamento experimental fatorial, 22 com triplicata no ponto central, mostrou que o modelo utilizado foi válido, e que o processo é favorecido com quantidades maiores de H2O2 em pH ácido. O tempo de equilíbrio para a fotodegradação do sulfametoxazol utilizando a placa de Zn recoberta com ZnO foi de 120 minutos com remoções de 95%, sob radiação artificial, seguindo uma lei de velocidade de pseudo-primeira ordem. A determinação de DQO e da concentração de nitrato indicaram que houve uma pequena mineralização do poluente, apesar da elevada remoção, mostrando que provavelmente houve a formação de espécies intermediárias. Além disso, a placa de zinco recoberta com ZnO apresentou uma eficiência catalítica praticamente inalterada em até 10 repetições de fotodegradação. No entanto, ao final do processo a concentração de zinco na amostra degradada estava acima da permitida pelos órgãos ambientais, sendo necessário a utilização de um pós-tratamento para a remoção do zinco ou a utilização de solução de sulfametoxazol com pH mais próximo da neutralidade para evitar a dissolução do metal do catalisador.

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Ziele dieser Dissertation sind die Aufklärung der Strömungsverhältnisse und Untersuchungen zum Verhalten von Arzneimittelrückständen im Tegeler See, die Entwicklung eines Simulationsmodells für Szenarioberechnungen sowie die Ableitung neuer Bewirtschaftungskonzepte unter Zuhilfenahme der gewonnenen Erkenntnisse und Modellergebnisse. Das zweidimensionale Strömungsmodell 2D-POM kann die Mischungsverhältnisse der beiden Zuflüsse zum Tegeler See, insbesondere den Einstrom der Oberhavel, ausreichend genau abbilden. Der Oberhaveleinstrom ist sowohl windinduziert als auch vom Abfluss der Oberhavel abhängig. Der Wind wirkt je nach Windrichtung verstärkend oder abschwächend auf den Oberhaveleinstrom. Der Tegeler See weist im Vergleich zu anderen Oberflächengewässern, die als Trinkwasserressource dienen, die höchsten bisher berichteten Gehalte an Arzneimittelrückständen auf. Die räumliche Verteilung von Carbamazepin (CBZ) und Sulfamethoxazol (SMX) wird hauptsächlich durch die Verdünnung mit Oberhavelwasser bestimmt. Nur ein geringer Teil des CBZ (40%) wird im Tegeler See eliminiert. Für SMX konnte keine Elimination festgestellt werden. Im Gegensatz dazu wird Diclofenac (DCF) im Oberflächenwasser photolytisch abgebaut (50% in den Wintermonaten, mehr als 95% im Sommer). Die Konzentrationen von DCF im Tegeler See zeigen deshalb eine hohe saisonale Variabilität. Durch Simulation von sieben Bewirtschaftungsszenarien wurde untersucht, ob mithilfe der existierenden Seeleitung und Phosphateliminierungsanlage die Konzentrationen der Arzneimittelrückstände im Tegeler See verringert werden können, ohne die erfolgreiche Seerestaurierung zu gefährden. In keinem Szenario konnten die Gehalte an Arzneimittelrückständen und Phosphor gleichzeitig auf einem akzeptablen Niveau gehalten werden. Aus diesem Grund sind ergänzende Maßnahmen notwendig, z.B. eine zusätzliche Spurenstoffentfernung im Zulauf des Sees oder eine weitere Phosphorreduzierung in der Oberhavel. / This cumulative thesis aims at (i) understanding the hydrodynamic characteristics of Lake Tegel, (ii) examining the occurrence and fate of pharmaceutical micro-pollutants in the lake, (iii) developing a modeling tool for scenario prediction, and (iv) utilizing the above findings and applying the above modeling tool to create new management strategies for Lake Tegel. The free-surface two-dimensional circulation model 2D-POM serves as an adequate tool for representing the intrusion of River Havel and the mixing intensity of both inflows, as validated by measured data. The calculations indicated that the intrusion of River Havel into Lake Tegel fluctuates with river discharge and wind, both of which can amplify or neutralize the other. Compared to other surface waters also used as drinking water resources, Lake Tegel seams to feature the highest ever reported pharmaceutical concentrations worldwide. The spatial distribution of carbamazepine (CBZ) and sulfamethoxazole (SMX) in the lake was shown to be primarily affected by dilution with water from River Havel rather than by degradation within the lake. By contrast, concentrations of diclofenac (DCL) are affected by both dilution and photodegradation. DCF showed the strongest elimination of all three pharmaceuticals and revealed significant seasonality with 50% elimination in winter and more than 95% in summer. Elimination of CBZ was 40%, while SMX did not degrade at determinable rates. Seven different management scenarios were tested to answer the question of whether the existing lake pipeline could be used to reduce the amount of pharmaceuticals in Lake Tegel without deteriorating the current phosphorus level. No scenario provided a strategy optimal for both pharmaceuticals and phosphorus. Consequently, additional efforts need to be made, such as supplementary pharmaceutical treatment of the inflow originating from the wastewater treatment plant, or phosphorus reduction in the River Havel catchment.