Compostos farmacêuticos são detectados em diversas matrizes ambientais. Estes compostos, quando não eliminados por técnicas avançadas de tratamento, contribuem para impactos ambientais negativos. Especificamente, efluentes hospitalares apresentam altas concentrações destes compostos principalmente pela excreção por pacientes. Neste contexto, o presente trabalho visa contribuir com a pesquisa científica em relação a efluentes hospitalares no Brasil, propondo alternativas de tratamento com ozônio para a remoção de fármacos. Para atingir o objetivo proposto, foi realizado um diagnóstico em um hospital visando identificar o consumo das principais classes farmacêuticas. A partir deste estudo, desenvolveu-se um planejamento de experimentos para avaliar os parâmetros mais adequados do processo de ozonização para a remoção de cafeína (CAF), amoxicilina (AMX) e ampicilina (AMP) em soluções aquosas. Foram avaliados experimentalmente os processos O3, O3/UV, O3/Fe2+, O3/UV/Fe2+. Investigou-se a influência da concentração inicial de fármaco, do pH, da potência de luz UV aplicada e da concentração inicial de Fe2+ utilizado como catalisador homogêneo. A variável de resposta foi a eficiência de mineralização. Os parâmetros obtidos pelo planejamento experimental foram aplicados para o Atenolol (ATE) e para soluções aquosas contendo a mistura de todos os compostos analisados (CAF, AMX, AMP e ATE). Um estudo cinético para determinação das constantes de reação foi realizado para a cafeína e atenolol. Para avaliar o tratamento com efluente hospitalar, uma caracterização (detecção de compostos farmacêuticos e parâmetros físico-químicos e toxicológicos) foi realizada antes e após o processo que apresentou a melhor eficiência de mineralização. Com o objetivo de extrapolar os estudos realizados e avaliar outros poluentes emergentes, além dos compostos farmacêuticos, realizaram-se experimentos com 90 compostos como drogas de abuso, hormônios e produtos de higiene pessoal que também podem estar presentes em efluentes hospitalares, avaliando a influência do pH e da dosagem de ozônio aplicada. Como principais resultados, os antibióticos e cardiovasculares foram as classes farmacêuticas mais consumidas no hospital. Pelo planejamento de experimentos, observou-se que todos os compostos avaliados foram rapidamente degradados (100% em menos de 15min) e as melhores eficiências de mineralização atingiram 70,8%, 60,4% e 63,6% para CAF, AMX e AMP, respectivamente. O sistema O3/UV/Fe2+ obteve a melhor eficiência de mineralização para o ATE (67,9%) e para a mistura dos compostos (69,5%). O estudo cinético possibilitou o cálculo das constantes cinéticas: kO3 =697,46 M-1 s-1 e kOH = 6,41x109 M-1 s-1 para a cafeína; e kO3 =146,56 M-1 s-1 e kOH = 15,29x109 M-1 s-1 para o atenolol. A eficiência de mineralização para os experimentos com efluente hospitalar atingiu 54,7% para o sistema O3/UV, sendo eficiente para a completa eliminação de diversos compostos farmacêuticos e remoção da toxicidade. Em relação à remoção dos 90 poluentes emergentes, observou-se que 53,3% dos compostos foram completamente degradados utilizando uma razão mMO3/mMC=0,3 em pH neutro. Os resultados encontrados indicam que o presente trabalho contribui para o avanço da pesquisa sobre efluentes hospitalares, pois apresenta uma alternativa de tratamento eficiente para a completa remoção de diversos compostos farmacêuticos, minimizando o impacto negativo destes no meio ambiente. / Pharmaceutical compounds (PhCs) are detected in various environmental matrices. These compounds, whether not eliminated by advanced treatment techniques, contribute to bacterial resistance and negative environmental impacts on water resource. Specifically, hospital wastewaster exhibit high concentrations of these compounds mainly by the excretion by patients. In this context, this paper aims to contribute to scientific research regarding hospital wastewater in Brazil, proposing treatment alternatives by ozone to remove PhCs. To achieve this purpose, it conducted a diagnosis in a hospital to identify the consumption of major pharmaceutical classes. With this result, it developed an experimental design to evaluate the most appropriate parameters of the ozonation process for the removal of caffeine (CAF), amoxicillin (AMX) and ampicillin (AMP) in aqueous solutions. This study evaluated the following processes experimentally: O3, O3/UV, O3/Fe2+ O3/UV/Fe2+. The influence of ozone dose, initial PhCs concentration, pH, power UV light applied and Fe2+ initial concentration used as homogeneous catalyst were investigated. Mineralization efficiency was the response variable. Parameters obtained by the experimental design were applied for Atenolol (ATE) and aqueous solutions containing the mixture of all compounds analyzed (CAF, AMX, AMP and ATE). A kinetic study for the determination of reaction constants was carried out for caffeine and atenolol. To evaluate the hospital wastewater treatment, a characterization (detection of pharmaceutical compounds and physico-chemical and toxicological parameters) was performed before and after the process that showed the best mineralization efficiency. In order to extrapolate the studies and evaluate other emergent pollutants, in addition to pharmaceutical compounds, were conducted experiments with 90 compounds such as illicit drugs, hormones and personal care products, which also may be present in hospital wastewater, evaluating the influence of pH and ozone dosage. Main results showed that antibiotics and cardiovascular were the most consumed pharmaceutical classes in the hospital. For the design of experiments, it was observed that all the evaluated compounds were rapidly degraded (100% in less than 15 minutes) and the best mineralization efficiency reached 70.8%, 60.4% and 63.6% for CAF and AMX AMP, respectively. The system O3/UV/Fe2+ obtained the best mineralization efficiency for ATE (67.9%) and mixture of compounds (69.5%). The kinetic study allowed the determination of the kinetic constants: kO3 = 697.46 M-1 s-1 and kOH = 6.41x109 M-1 s-1 for caffeine; and kO3 = 146.56 M-1 s-1 and kOH = 15.29x109 M-1 s-1 for atenolol. Mineralization efficiency for hospital wastewater experiments reached 54.7% by the system O3/UV, being efficient for complete elimination of various PhCs and removal of toxicity. Regarding the removal of 90 emergent pollutants, it was observed that 53.3% of the compounds were completely degraded using a ratio mMO3/MMC = 0.3 at neutral pH. The results indicated that this work contributes to the advance of research on hospital wastewater, because it presents an effective alternative treatment for complete removal of various pharmaceutical compounds, minimizing the negative impact on the environment.

<p>Analytical analyses conducted at the Himmerfjärden WWTP (285.000 PE connected) identified 70 pharmaceutical compounds belonging to different therapeutic classes. Such organic micropollutants at low detected concentration range of µg - ng l^-1 did not affect the treatment processes at WWTP. Results from analytical studies indicated continuous discharge of organic micropollutants to the surface water with a calculated load amounting to 1.51 kg day-1. Metoprolol, carbamazepine and naproxen were chosen for testing different removal methods. Oxygen Uptake Rate (OUR) tests were conducted to assess the bacterial activity of an activated sludge taken from a full scale aeration plant with the presence of selected target compounds.</p><p>A semi-technical scale membrane bioreactor ZeeWeed10™, treating final effluent from the Himmerfjärden WWTP (Sweden) was seeded with activated sludge from full scale biological stage. The membrane bioreactor (MBR) system placed after the final treatment appeared to be an insufficient technology for removal of residual amounts of organic micropollutants from WWTP effluents. Batch test studies with activated sludge taken from the membrane bioreactor and with application of granular activated carbon (GAC) filtration resulted in giving an overall assessment of removal efficiency. Metoprolol and carbamazepine tend to be resistant to the biodegradation process and in the dosed high concentration lead to bacterial cell decomposition in the activated sludge. Apparently, removal efficiency for naproxen exceeded the value of 46% with the spiked initial amount of 3.3 mg NAP g^-1MLSS. Application of the GAC filtration proved to be an efficient technique for removal of pharmaceutical compounds from treated wastewater.</p><p>Application of the statistical programme Modde7 was a time saving tool in studies of fouling occurrence. The effect of fouling phenomenon, which is a highly limiting factor for MBR performance, was minimised by adjusting the operational parameters as predicted by the Modde7 programme.</p>

Precipitation with a Compressed Fluid Antisolvent (PCA) and Rapid Expansion from Supercritical Solution (RESS) are two processes based on supercritical fluids that are capable of producing submicron particles. Novel variations of these basic processes have been examined to produce stable particles of various pharmaceutical compounds. PCA is an antisolvent precipitation technique where an organic solution of drug + polymer in solvent is atomized (sprayed) into supercritical (SC) CO₂. Upon liquid mixing, the solute materials precipitate to form microparticles. A Vapor-over-Liquid technique has been used to produce larger, uniform particle sizes of biodegradable polymers. By suspending a protein in the solvent phase, the protein can be encapsulated/coated by the precipitating polymer. RESS is a process by which a homogeneous solution at supercritical conditions is sprayed through an expansion nozzle to atmospheric conditions. The resultant change in phase leads to the precipitation of the solute materials. The production of extremely small particles (<50 nm) have been predicted but rarely demonstrated. Typically, particle growth occurs to form larger (~1 μm) particles. A novel adaptation was developed, dubbed RESAS (Rapid Expansion from Supercritical to Aqueous Solution), wherein the expansion is conducted within an aqueous environment. The aqueous phase can contain surfactant or lipid stabilizers to capture and preserve submicron particles of water-insoluble drug actives in the form of a suspension. / text

Compostos farmacêuticos são detectados em diversas matrizes ambientais. Estes compostos, quando não eliminados por técnicas avançadas de tratamento, contribuem para impactos ambientais negativos. Especificamente, efluentes hospitalares apresentam altas concentrações destes compostos principalmente pela excreção por pacientes. Neste contexto, o presente trabalho visa contribuir com a pesquisa científica em relação a efluentes hospitalares no Brasil, propondo alternativas de tratamento com ozônio para a remoção de fármacos. Para atingir o objetivo proposto, foi realizado um diagnóstico em um hospital visando identificar o consumo das principais classes farmacêuticas. A partir deste estudo, desenvolveu-se um planejamento de experimentos para avaliar os parâmetros mais adequados do processo de ozonização para a remoção de cafeína (CAF), amoxicilina (AMX) e ampicilina (AMP) em soluções aquosas. Foram avaliados experimentalmente os processos O3, O3/UV, O3/Fe2+, O3/UV/Fe2+. Investigou-se a influência da concentração inicial de fármaco, do pH, da potência de luz UV aplicada e da concentração inicial de Fe2+ utilizado como catalisador homogêneo. A variável de resposta foi a eficiência de mineralização. Os parâmetros obtidos pelo planejamento experimental foram aplicados para o Atenolol (ATE) e para soluções aquosas contendo a mistura de todos os compostos analisados (CAF, AMX, AMP e ATE). Um estudo cinético para determinação das constantes de reação foi realizado para a cafeína e atenolol. Para avaliar o tratamento com efluente hospitalar, uma caracterização (detecção de compostos farmacêuticos e parâmetros físico-químicos e toxicológicos) foi realizada antes e após o processo que apresentou a melhor eficiência de mineralização. Com o objetivo de extrapolar os estudos realizados e avaliar outros poluentes emergentes, além dos compostos farmacêuticos, realizaram-se experimentos com 90 compostos como drogas de abuso, hormônios e produtos de higiene pessoal que também podem estar presentes em efluentes hospitalares, avaliando a influência do pH e da dosagem de ozônio aplicada. Como principais resultados, os antibióticos e cardiovasculares foram as classes farmacêuticas mais consumidas no hospital. Pelo planejamento de experimentos, observou-se que todos os compostos avaliados foram rapidamente degradados (100% em menos de 15min) e as melhores eficiências de mineralização atingiram 70,8%, 60,4% e 63,6% para CAF, AMX e AMP, respectivamente. O sistema O3/UV/Fe2+ obteve a melhor eficiência de mineralização para o ATE (67,9%) e para a mistura dos compostos (69,5%). O estudo cinético possibilitou o cálculo das constantes cinéticas: kO3 =697,46 M-1 s-1 e kOH = 6,41x109 M-1 s-1 para a cafeína; e kO3 =146,56 M-1 s-1 e kOH = 15,29x109 M-1 s-1 para o atenolol. A eficiência de mineralização para os experimentos com efluente hospitalar atingiu 54,7% para o sistema O3/UV, sendo eficiente para a completa eliminação de diversos compostos farmacêuticos e remoção da toxicidade. Em relação à remoção dos 90 poluentes emergentes, observou-se que 53,3% dos compostos foram completamente degradados utilizando uma razão mMO3/mMC=0,3 em pH neutro. Os resultados encontrados indicam que o presente trabalho contribui para o avanço da pesquisa sobre efluentes hospitalares, pois apresenta uma alternativa de tratamento eficiente para a completa remoção de diversos compostos farmacêuticos, minimizando o impacto negativo destes no meio ambiente. / Pharmaceutical compounds (PhCs) are detected in various environmental matrices. These compounds, whether not eliminated by advanced treatment techniques, contribute to bacterial resistance and negative environmental impacts on water resource. Specifically, hospital wastewaster exhibit high concentrations of these compounds mainly by the excretion by patients. In this context, this paper aims to contribute to scientific research regarding hospital wastewater in Brazil, proposing treatment alternatives by ozone to remove PhCs. To achieve this purpose, it conducted a diagnosis in a hospital to identify the consumption of major pharmaceutical classes. With this result, it developed an experimental design to evaluate the most appropriate parameters of the ozonation process for the removal of caffeine (CAF), amoxicillin (AMX) and ampicillin (AMP) in aqueous solutions. This study evaluated the following processes experimentally: O3, O3/UV, O3/Fe2+ O3/UV/Fe2+. The influence of ozone dose, initial PhCs concentration, pH, power UV light applied and Fe2+ initial concentration used as homogeneous catalyst were investigated. Mineralization efficiency was the response variable. Parameters obtained by the experimental design were applied for Atenolol (ATE) and aqueous solutions containing the mixture of all compounds analyzed (CAF, AMX, AMP and ATE). A kinetic study for the determination of reaction constants was carried out for caffeine and atenolol. To evaluate the hospital wastewater treatment, a characterization (detection of pharmaceutical compounds and physico-chemical and toxicological parameters) was performed before and after the process that showed the best mineralization efficiency. In order to extrapolate the studies and evaluate other emergent pollutants, in addition to pharmaceutical compounds, were conducted experiments with 90 compounds such as illicit drugs, hormones and personal care products, which also may be present in hospital wastewater, evaluating the influence of pH and ozone dosage. Main results showed that antibiotics and cardiovascular were the most consumed pharmaceutical classes in the hospital. For the design of experiments, it was observed that all the evaluated compounds were rapidly degraded (100% in less than 15 minutes) and the best mineralization efficiency reached 70.8%, 60.4% and 63.6% for CAF and AMX AMP, respectively. The system O3/UV/Fe2+ obtained the best mineralization efficiency for ATE (67.9%) and mixture of compounds (69.5%). The kinetic study allowed the determination of the kinetic constants: kO3 = 697.46 M-1 s-1 and kOH = 6.41x109 M-1 s-1 for caffeine; and kO3 = 146.56 M-1 s-1 and kOH = 15.29x109 M-1 s-1 for atenolol. Mineralization efficiency for hospital wastewater experiments reached 54.7% by the system O3/UV, being efficient for complete elimination of various PhCs and removal of toxicity. Regarding the removal of 90 emergent pollutants, it was observed that 53.3% of the compounds were completely degraded using a ratio mMO3/MMC = 0.3 at neutral pH. The results indicated that this work contributes to the advance of research on hospital wastewater, because it presents an effective alternative treatment for complete removal of various pharmaceutical compounds, minimizing the negative impact on the environment.

Compostos farmacêuticos são detectados em diversas matrizes ambientais. Estes compostos, quando não eliminados por técnicas avançadas de tratamento, contribuem para impactos ambientais negativos. Especificamente, efluentes hospitalares apresentam altas concentrações destes compostos principalmente pela excreção por pacientes. Neste contexto, o presente trabalho visa contribuir com a pesquisa científica em relação a efluentes hospitalares no Brasil, propondo alternativas de tratamento com ozônio para a remoção de fármacos. Para atingir o objetivo proposto, foi realizado um diagnóstico em um hospital visando identificar o consumo das principais classes farmacêuticas. A partir deste estudo, desenvolveu-se um planejamento de experimentos para avaliar os parâmetros mais adequados do processo de ozonização para a remoção de cafeína (CAF), amoxicilina (AMX) e ampicilina (AMP) em soluções aquosas. Foram avaliados experimentalmente os processos O3, O3/UV, O3/Fe2+, O3/UV/Fe2+. Investigou-se a influência da concentração inicial de fármaco, do pH, da potência de luz UV aplicada e da concentração inicial de Fe2+ utilizado como catalisador homogêneo. A variável de resposta foi a eficiência de mineralização. Os parâmetros obtidos pelo planejamento experimental foram aplicados para o Atenolol (ATE) e para soluções aquosas contendo a mistura de todos os compostos analisados (CAF, AMX, AMP e ATE). Um estudo cinético para determinação das constantes de reação foi realizado para a cafeína e atenolol. Para avaliar o tratamento com efluente hospitalar, uma caracterização (detecção de compostos farmacêuticos e parâmetros físico-químicos e toxicológicos) foi realizada antes e após o processo que apresentou a melhor eficiência de mineralização. Com o objetivo de extrapolar os estudos realizados e avaliar outros poluentes emergentes, além dos compostos farmacêuticos, realizaram-se experimentos com 90 compostos como drogas de abuso, hormônios e produtos de higiene pessoal que também podem estar presentes em efluentes hospitalares, avaliando a influência do pH e da dosagem de ozônio aplicada. Como principais resultados, os antibióticos e cardiovasculares foram as classes farmacêuticas mais consumidas no hospital. Pelo planejamento de experimentos, observou-se que todos os compostos avaliados foram rapidamente degradados (100% em menos de 15min) e as melhores eficiências de mineralização atingiram 70,8%, 60,4% e 63,6% para CAF, AMX e AMP, respectivamente. O sistema O3/UV/Fe2+ obteve a melhor eficiência de mineralização para o ATE (67,9%) e para a mistura dos compostos (69,5%). O estudo cinético possibilitou o cálculo das constantes cinéticas: kO3 =697,46 M-1 s-1 e kOH = 6,41x109 M-1 s-1 para a cafeína; e kO3 =146,56 M-1 s-1 e kOH = 15,29x109 M-1 s-1 para o atenolol. A eficiência de mineralização para os experimentos com efluente hospitalar atingiu 54,7% para o sistema O3/UV, sendo eficiente para a completa eliminação de diversos compostos farmacêuticos e remoção da toxicidade. Em relação à remoção dos 90 poluentes emergentes, observou-se que 53,3% dos compostos foram completamente degradados utilizando uma razão mMO3/mMC=0,3 em pH neutro. Os resultados encontrados indicam que o presente trabalho contribui para o avanço da pesquisa sobre efluentes hospitalares, pois apresenta uma alternativa de tratamento eficiente para a completa remoção de diversos compostos farmacêuticos, minimizando o impacto negativo destes no meio ambiente. / Pharmaceutical compounds (PhCs) are detected in various environmental matrices. These compounds, whether not eliminated by advanced treatment techniques, contribute to bacterial resistance and negative environmental impacts on water resource. Specifically, hospital wastewaster exhibit high concentrations of these compounds mainly by the excretion by patients. In this context, this paper aims to contribute to scientific research regarding hospital wastewater in Brazil, proposing treatment alternatives by ozone to remove PhCs. To achieve this purpose, it conducted a diagnosis in a hospital to identify the consumption of major pharmaceutical classes. With this result, it developed an experimental design to evaluate the most appropriate parameters of the ozonation process for the removal of caffeine (CAF), amoxicillin (AMX) and ampicillin (AMP) in aqueous solutions. This study evaluated the following processes experimentally: O3, O3/UV, O3/Fe2+ O3/UV/Fe2+. The influence of ozone dose, initial PhCs concentration, pH, power UV light applied and Fe2+ initial concentration used as homogeneous catalyst were investigated. Mineralization efficiency was the response variable. Parameters obtained by the experimental design were applied for Atenolol (ATE) and aqueous solutions containing the mixture of all compounds analyzed (CAF, AMX, AMP and ATE). A kinetic study for the determination of reaction constants was carried out for caffeine and atenolol. To evaluate the hospital wastewater treatment, a characterization (detection of pharmaceutical compounds and physico-chemical and toxicological parameters) was performed before and after the process that showed the best mineralization efficiency. In order to extrapolate the studies and evaluate other emergent pollutants, in addition to pharmaceutical compounds, were conducted experiments with 90 compounds such as illicit drugs, hormones and personal care products, which also may be present in hospital wastewater, evaluating the influence of pH and ozone dosage. Main results showed that antibiotics and cardiovascular were the most consumed pharmaceutical classes in the hospital. For the design of experiments, it was observed that all the evaluated compounds were rapidly degraded (100% in less than 15 minutes) and the best mineralization efficiency reached 70.8%, 60.4% and 63.6% for CAF and AMX AMP, respectively. The system O3/UV/Fe2+ obtained the best mineralization efficiency for ATE (67.9%) and mixture of compounds (69.5%). The kinetic study allowed the determination of the kinetic constants: kO3 = 697.46 M-1 s-1 and kOH = 6.41x109 M-1 s-1 for caffeine; and kO3 = 146.56 M-1 s-1 and kOH = 15.29x109 M-1 s-1 for atenolol. Mineralization efficiency for hospital wastewater experiments reached 54.7% by the system O3/UV, being efficient for complete elimination of various PhCs and removal of toxicity. Regarding the removal of 90 emergent pollutants, it was observed that 53.3% of the compounds were completely degraded using a ratio mMO3/MMC = 0.3 at neutral pH. The results indicated that this work contributes to the advance of research on hospital wastewater, because it presents an effective alternative treatment for complete removal of various pharmaceutical compounds, minimizing the negative impact on the environment.

Analytical analyses conducted at the Himmerfjärden WWTP (285.000 PE connected) identified 70 pharmaceutical compounds belonging to different therapeutic classes. Such organic micropollutants at low detected concentration range of µg - ng l-1 did not affect the treatment processes at WWTP. Results from analytical studies indicated continuous discharge of organic micropollutants to the surface water with a calculated load amounting to 1.51 kg day-1. Metoprolol, carbamazepine and naproxen were chosen for testing different removal methods. Oxygen Uptake Rate (OUR) tests were conducted to assess the bacterial activity of an activated sludge taken from a full scale aeration plant with the presence of selected target compounds. A semi-technical scale membrane bioreactor ZeeWeed10™, treating final effluent from the Himmerfjärden WWTP (Sweden) was seeded with activated sludge from full scale biological stage. The membrane bioreactor (MBR) system placed after the final treatment appeared to be an insufficient technology for removal of residual amounts of organic micropollutants from WWTP effluents. Batch test studies with activated sludge taken from the membrane bioreactor and with application of granular activated carbon (GAC) filtration resulted in giving an overall assessment of removal efficiency. Metoprolol and carbamazepine tend to be resistant to the biodegradation process and in the dosed high concentration lead to bacterial cell decomposition in the activated sludge. Apparently, removal efficiency for naproxen exceeded the value of 46% with the spiked initial amount of 3.3 mg NAP g-1 MLSS. Application of the GAC filtration proved to be an efficient technique for removal of pharmaceutical compounds from treated wastewater. Application of the statistical programme Modde7 was a time saving tool in studies of fouling occurrence. The effect of fouling phenomenon, which is a highly limiting factor for MBR performance, was minimised by adjusting the operational parameters as predicted by the Modde7 programme. / QC 20101104

O relevante conceito de sustentabilidade dos dias atuais leva a população a pensar no tratamento dos recursos naturais e principalmente na qualidade e escassez da água. A grave problemática quanto à gestão dos resíduos urbanos no país, desde sua produção, coleta e disposição final são os desafios colocado aos municípios e a sociedade em geral. O uso cada vez mais abundante dos medicamentos farmacêuticos gera uma demanda de resíduos que acabam atingindo os leitos dos rios. Com avanço das tecnologias é possível monitorar e conhecer os resíduos que afetam indiretamente e diretamente as águas das bacias hidrográficas. O objetivo deste trabalho foi desenvolver e validar uma metodologia analítica para a determinação dos resíduos de fármacos (ácido acetil salicílico, diclorofenaco de sódio, paracetamol, ibuprofeno e fenoprofeno) em águas utilizando a cromatografia líquida de ultra performance acoplada à espectrometria de massas tipo tandem (UPLC-MS/MS). Foram utilizadas duas fases moveis distintas. Para os fármacos paracetamol e diclofenaco foi utilizado como fase móvel água: metanol (1:1; V/V) com adição de ácido fórmico e a ionização de eletrospray em modo positivo; para os fármacos acetil salicílico, ibuprofeno e fenoprofeno foi utilizado água: metanol (1:1; v/v) com adição de acetato de amônio e a ionização de eletrospray em modo negativo. O desempenho do método foi avaliado quanto aos seguintes parâmetros: especificidade e seletividade, faixa de trabalho, linearidade; limite de detecção e limite de quantificação, exatidão, robustez e incerteza de medição. Os resultados obtidos comprovaram a adequabilidade do método ao propósito supracitado. Os valores obtidos para o limite de decisão (cc&alpha;) e capabilidade de detecção (cc&beta;) foram: paracetamol 0,21 e 0,34 &mu;g L -1; diclofenaco 2,42 e 3,24 &mu;g L -1 ; AAS 1,56 e 2,45 &mu;g L -1; ibuprofeno 2,34 e 3,21 &mu;g L -1 e fenoprofeno 1,89 e 2,33 &mu;g L-1, respectivamente. A metodologia foi aplicada na caracterização de amostras de água superficial (bruta) e tratada proveniente de áreas de captação e de tratamento de água da bacia hidrográfica do Paraíba do Sul. Foram realizadas duas coletas distintas, setembro/ 2010 e novembro/ 2010, nos municípios de Guararema, São José dos Campos, Taubaté e Pindamonhangaba. Em 31,2 % das amostras, Cinco amostras de água bruta das 16 amostras analisadas, foram encontrados resíduos de paracetamol. Os resultados obtidos apresentaram-se em uma faixa de concentração de 0,10 a 0,50 &mu;g L -1. / The relevant concept of sustainability of the present day leads people to think about the treatment of natural resources and particularly in the quanlity and scarcity of water. The serious problems regarding the management of municipal waste in the country, from production, collection and disposal are the challenges facing municipalities and society in general. The increasing use of pharmaceutical drugs most abundant generates a demand for waste that eventually reach the river beds. With advancement of technologies and know you can monitor the waste that directly and indirectly affect the waters of river basins. The objective of this study was to develop and validade analytical methods for residues of drugs (aspirin, sodium diclofenac, paracetamol, ibuprofen and fenoprofen) in water using ultra performance liquida chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). We used two different mobile phases. For the drugs paracetamol and diclofenac was used as mobile phase water:methanol (1:1, v/v) with addition of formic acid in positive electrospray ionization mode. For drugs acetyl salicylic acid, ibuprofen and fenoprofen was used mobile phase water:methanol (1:1, v/v) with addition of ammonium acetate and negative electrospray ionization mode. The performance of the method was evaluated on the following parameters: specificity and selectivity, working range, lineariry, limit of detection and limit of quantification, accuracy, ruggedness and uncertainty measurement. The result obtained proved the suitability of the method for fit purpose. The values obtained for the decision limit (cc&alpha;) and detection capability (cc&beta;) were 0.21 and 0.34 &mu;g L-1, diclofenac 2.42 and 3.24 &mu;gL-1, ASA 1.56 and 2.45 &mu;gL-1, respectively. The methodology was applied in the characterization of samples of surface water (raw) and treated from catchment areas and water treatment basin of Paraíba do sul were two distinct collections, September/2011 and November 2010 in the municipalities of Guararema, São José dos Campos, Taubaté and Pindamonhangaba. In 32,2% of all samples, five samples of 16 raw water samples, residues were found for paracetamol. The results were presented in a concentration range from 0.10 to 0.50 &mu;g L-1.

O relevante conceito de sustentabilidade dos dias atuais leva a população a pensar no tratamento dos recursos naturais e principalmente na qualidade e escassez da água. A grave problemática quanto à gestão dos resíduos urbanos no país, desde sua produção, coleta e disposição final são os desafios colocado aos municípios e a sociedade em geral. O uso cada vez mais abundante dos medicamentos farmacêuticos gera uma demanda de resíduos que acabam atingindo os leitos dos rios. Com avanço das tecnologias é possível monitorar e conhecer os resíduos que afetam indiretamente e diretamente as águas das bacias hidrográficas. O objetivo deste trabalho foi desenvolver e validar uma metodologia analítica para a determinação dos resíduos de fármacos (ácido acetil salicílico, diclorofenaco de sódio, paracetamol, ibuprofeno e fenoprofeno) em águas utilizando a cromatografia líquida de ultra performance acoplada à espectrometria de massas tipo tandem (UPLC-MS/MS). Foram utilizadas duas fases moveis distintas. Para os fármacos paracetamol e diclofenaco foi utilizado como fase móvel água: metanol (1:1; V/V) com adição de ácido fórmico e a ionização de eletrospray em modo positivo; para os fármacos acetil salicílico, ibuprofeno e fenoprofeno foi utilizado água: metanol (1:1; v/v) com adição de acetato de amônio e a ionização de eletrospray em modo negativo. O desempenho do método foi avaliado quanto aos seguintes parâmetros: especificidade e seletividade, faixa de trabalho, linearidade; limite de detecção e limite de quantificação, exatidão, robustez e incerteza de medição. Os resultados obtidos comprovaram a adequabilidade do método ao propósito supracitado. Os valores obtidos para o limite de decisão (cc&alpha;) e capabilidade de detecção (cc&beta;) foram: paracetamol 0,21 e 0,34 &mu;g L -1; diclofenaco 2,42 e 3,24 &mu;g L -1 ; AAS 1,56 e 2,45 &mu;g L -1; ibuprofeno 2,34 e 3,21 &mu;g L -1 e fenoprofeno 1,89 e 2,33 &mu;g L-1, respectivamente. A metodologia foi aplicada na caracterização de amostras de água superficial (bruta) e tratada proveniente de áreas de captação e de tratamento de água da bacia hidrográfica do Paraíba do Sul. Foram realizadas duas coletas distintas, setembro/ 2010 e novembro/ 2010, nos municípios de Guararema, São José dos Campos, Taubaté e Pindamonhangaba. Em 31,2 % das amostras, Cinco amostras de água bruta das 16 amostras analisadas, foram encontrados resíduos de paracetamol. Os resultados obtidos apresentaram-se em uma faixa de concentração de 0,10 a 0,50 &mu;g L -1. / The relevant concept of sustainability of the present day leads people to think about the treatment of natural resources and particularly in the quanlity and scarcity of water. The serious problems regarding the management of municipal waste in the country, from production, collection and disposal are the challenges facing municipalities and society in general. The increasing use of pharmaceutical drugs most abundant generates a demand for waste that eventually reach the river beds. With advancement of technologies and know you can monitor the waste that directly and indirectly affect the waters of river basins. The objective of this study was to develop and validade analytical methods for residues of drugs (aspirin, sodium diclofenac, paracetamol, ibuprofen and fenoprofen) in water using ultra performance liquida chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). We used two different mobile phases. For the drugs paracetamol and diclofenac was used as mobile phase water:methanol (1:1, v/v) with addition of formic acid in positive electrospray ionization mode. For drugs acetyl salicylic acid, ibuprofen and fenoprofen was used mobile phase water:methanol (1:1, v/v) with addition of ammonium acetate and negative electrospray ionization mode. The performance of the method was evaluated on the following parameters: specificity and selectivity, working range, lineariry, limit of detection and limit of quantification, accuracy, ruggedness and uncertainty measurement. The result obtained proved the suitability of the method for fit purpose. The values obtained for the decision limit (cc&alpha;) and detection capability (cc&beta;) were 0.21 and 0.34 &mu;g L-1, diclofenac 2.42 and 3.24 &mu;gL-1, ASA 1.56 and 2.45 &mu;gL-1, respectively. The methodology was applied in the characterization of samples of surface water (raw) and treated from catchment areas and water treatment basin of Paraíba do sul were two distinct collections, September/2011 and November 2010 in the municipalities of Guararema, São José dos Campos, Taubaté and Pindamonhangaba. In 32,2% of all samples, five samples of 16 raw water samples, residues were found for paracetamol. The results were presented in a concentration range from 0.10 to 0.50 &mu;g L-1.

L’objectif de ce travail a consisté à évaluer différents effets écotoxiques, cytotoxique et le potentiel androgénique de 14 produits pharmaceutiques: la clomipramine, la fluoxétine, la fluvoxamine, la paroxétine, la sertraline et la venlafaxine (antidépresseurs), l’amphotéricine B, l’éconazole, le kétoconazole et le miconazole (antifongiques), la clarithromycine (antibiotique), l’acébutolol (ß-bloquants), le gabapentine (antiépileptiques) et la cétirizine (antihistaminiques), à l’aide d’études in vivo et in vitro. Les tests d’écotoxicité aiguë (96h) sur le cnidaire d’eau douce Hydra attenuata ont montré un effet délétère sur la survie des hydres adultes, la morphologie et le développement des embryons pour l’ensemble d’antidépresseurs et des antifongiques testés. Les valeurs de CE50 calculées ont révélé que l’éconazole, le miconazole et la sertraline sont les molécules les plus toxiques. Les tests d’écotoxicité chronique sur les hydres adultes (10 jours) et les embryons (14 jours) ont mis en évidence que la plus part des molécules d’antidépresseurs testées sont des embryotoxiques et tératogènes puisque ils induisent des malformations chez les embryons contrairement aux antifongiques qui présentent des anomalies seulement chez les adultes. Ces tests ont montré aussi que les molécules d’antidépresseurs testées seules sont moins toxiques que lorsqu’elles sont testées en mélange. En effet, le mélange de molécules antidépresseurs testées présente une toxicité plus élevée sur les adultes que sur les embryons, avec une concentration minimale induisant des effets significatifs de l’ordre de ng L-1, concentrations proches de celles retrouvées dans l’environnement. De plus, les résultats d’écotoxicité chronique sur plusieurs générations d’hydres ont montré que la morphologie des individus de la première génération (F0) ainsi que ceux de la deuxième génération (F1) été affectée de la même manière, démontrant une sensibilité du même ordre vis-à-vis de la sertraline ou du mélange d’antidépresseurs, tandis que les individus issus de la troisième génération (F2) apparaissent moins sensibles lors de l'exposition à la sertraline. Par contre, la reproduction des hydres exposées à la sertraline est diminué de plus en plus dans chaque génération, avec une toxicité plus importante pour les individus de la troisième génération. Le mélange d’antidépresseurs affecte la reproduction des hydres de la deuxième génération F1 à des concentrations environnementales. Les essais in vitro conduits sur les mêmes molécules pharmaceutiques, testées seules et en mélange, sur les cellules MDA-Kb2 n'ont révélé aucun effet androgénique et cytotoxique sur les cellules à des concentrations environnementales / The objective of this work was to evaluate different ecotoxic, cytotoxic and androgenic effects of 14 pharmaceutical compounds: clomipramine, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine, amphotericin B, éconazole, ketoconazole and miconazole, clarithromycin, the acebutolol, gabapentin and cetirizine, using in vivo and in vitro studies. The acute ecotoxicity tests (96h) on the freshwater cnidarian Hydra attenuata showed deleterious effects on adult survival, morphology and embryo development for all tested antidepressants and antifungals drug. The values of EC50 concentrations revealed that econazole, miconazole and sertraline are the most toxic molecules. The chronic ecotoxicity tests on hydras adults (10 days) and embryos (14 days) revealed that most of the molecules tested antidepressants are embryotoxic and teratogenic as they cause malformations in embryos contrary to antifungal which display abnormalities in adults only. These tests also showed that antidepressants tested individually are less toxic than when tested as a mixture. This mixture has a higher toxicity on adults than on embryos, with significant effects concentrations around ng L-1 which are close to measured environmental concentrations. In addition, chronic ecotoxicity results over several generations of hydras have shown identical sensitivity of both first and second generation on morphology of individuals. No more toxicity was observed on the third generation of hydra. Concerning the reproduction of hydras, this parameters was strongly decreased in all generations with an increasing sensitivity of individuals along the generations. Moreover, the mixture of antidepressants affect reproduction of hydras for the second generation at environmental concentrations. In vitro tests conducted on MDA-KB2 cells with the same pharmaceuticals revealed that these compounds tested did not exert any androgenic and cytotoxic effect on cells in culture at environmental concentrations

Les hôpitaux génèrent des effluents riches en résidus pharmaceutiques (RP), fonctions de leurs activités de soins et de diagnostic. Certains de ces RP sont aujourd’hui retrouvés de manière ubiquitaire dans les écosystèmes aquatiques, en raison de leurs propriétés persistantes et/ou de leur émission continue. La variété de ces RP est telle qu’il est nécessaire de les hiérarchiser, en fonction des risques qu’ils représentent pour l’Environnement, à des fins d’étude et de gestion. Un de ces risques est le transfert des RP bioaccumulables (i.e. Kow élevé et faible biodégradabilité) dans les chaînes alimentaires, via les processus de bioconcentration, de bioaccumulation et de bioamplification. L’objectif principal de cette thèse est de caractériser expérimentalement la bioconcentration et la bioaccumulation de molécules identifiées comme prioritaires dans des travaux précédents. Le composé modèle que nous avons choisi est le tamoxifen, molécule utilisée contre le cancer du sein et déjà retrouvé dans l’Environnement. Les organismes étudiés, issus des trois niveaux trophiques de la chaine alimentaire modèle, sont Pseudokirchneriella subcapitata, Daphnia magna et Danio rerio. Pour mesurer la teneur de cette molécule dans les organismes, nous avons développé une méthode d’analyse reposant sur l’utilisation d’une molécule marquée par un isotope stable, le 15N tamoxifen.Nous avons mesuré des facteurs de bioconcentration (BCF) allant de 12800 chez D. magna à 85600 dans le foie de D. rerio en passant par 21500 chez P. subcapitata. Chez ces derniers, nous avons également évalué la part du régime alimentaire dans la bioaccumulation du tamoxifen. Nous avons observé que plus la concentration dans le milieu d’exposition est faible, plus le régime alimentaire contribue à la bioaccumulation. Ces travaux de thèse présentent de nombreuses perspectives que l’on peut regrouper autour de deux axes : connaissance de l’écotoxicité des RP et de l’écotoxicologie isotopique. / Hospitals generates effluents rich in pharmaceuticals compounds (PC), notably because of careand diagnostics activities. Some of these PCs are ubiquitous in aquatic ecosystems owing to itspersistent properties and/or because of continuous releasing in environment. The diversity of thesePCs is so strong that it is necessary to prioritize them, considering risks that PCs represents forthe Environment, in order to manage and study these compounds. One of these risks is the transferof bioaccumulatives PCs (i.e. PCs with high Kow and low biodegradability) along trophic webs,via bioconcentration, bioaccumulation and biomagnification processes. The main objective of thisthesis is to characterize bioconcentration and bioaccumulation of molecules identified as priorityin previous studies. The model compound choose in our work is the tamoxifen, a molecule usedin the treatment of breast cancer and already found in Environment. Organisms studied, typicalfrom three trophic levels of the model trophic chain, are Pseudokirchneriella subcapitata, Daphniamagna and Danio rerio. In order to measure content of tamoxifen in organisms, we developed aninnovative analytic method based on the use of stable isotopes labelled tamoxifen : 15N tamoxifen.We succeeded to measure bioconcentration factors (BCF) from 12800 in D. magna to 85600 in liverof D. rerio including BCF of 21500 in P. subcapitata. In this latter, we also assessed the contributionof dietary route to the total contamination of D. magna by tamoxifen. We observed that the morethe medium concentration was weak, the more the dietary route contribute to the contamination.These works shows numerous perspectives that we can gather inside two axes : ecotoxicity knowledgeof PCs an isotopic ecotoxicology.