A novel technique comprising solid phase microextraction and gas chromatography has been developed to analyse the three methylamines (monomethylamine, dimethylamine and trimethylamine) at the concentrations expected in seawater. The volatility of the methylamines was exploited and allowed the headspace pre-concentration and gas chromatographic separation of the analytes. This method achieved limits of detection of 0.43 nmol dm-3, 2.50 nmol dm-3 and 0.37 nmol dm-3 for monomethylamine, dimethylamine and trimethylamine, respectively, which are lower than any previously reported for seawater. This technique was applied to natural samples collected from the Western English Channel (WEC) and the methylamines were successfully quantified. A liquid chromatography-mass spectrometry method was used to analyse glycine betaine in marine particulates. The volume filtered during sample collection was found to be critical in achieving accurate measurements of glycine betaine. Large filter volumes (1 L) significantly decreased observed concentrations compared to smaller volumes, and 10 mL was the optimised amount filtered. The difference in concentrations was attributed to large water volumes causing cell damage and loss of glycine betaine to the dissolved phase. Cell resilience was thought to play a role in the differences observed; for example, diatoms with their rigid silica cell walls were hypothesised to be more resilient to filtration stress. A seasonal study was carried out in the WEC using both 1 L and 10 mL samples and maximum glycine betaine concentrations were 50 nmol dm-3 and 484 nmol dm-3 in the 1 L and 10 mL samples, respectively. The latter concentrations were more than an order of magnitude higher than all previous measurements. Seasonality was observed and a significant correlation was found with chlorophyll a. Statistics were applied to the phytoplankton biomass data and contributions from specific phytoplankton taxa were identified, including from Prorocentrum minimum and Chaetoceros socialis.

Les zones de cisaillement constituent des objets structuraux communs de la lithosphère. À grande échelle, elles sont le siège principal des déplacements entre plaques tectoniques, accommodant de grandes quantités de déformation. La compréhension de leur comportement mécanique dans le temps et l'espace est donc essentielle pour la connaissance générale de la dynamique de la lithosphère. La température joue un rôle majeur sur la loi de comportement rhéologique qui caractérise le domaine ductile (en profondeur), réduisant alors efficacement la résistance mécanique. Chaque roche possède en outre des propriétés mécaniques intrinsèques qui varient en fonction de sa composition minéralogique, de sa texture et de sa structure interne. Or, en l'absence de grandeurs directement mesurables en profondeur, la rhéologie de la lithosphère demeure sujette à diverses interprétations. Le comportement mécanique des zones de cisaillement est d'autant plus méconnu qu'elles sont le siège d'intenses changements de la nature des roches et de perturbations thermiques majeures. En particulier, l'énergie mécanique qui y est convertie en chaleur (shear heating) peut engendrer une étroite interrelation entre thermique et mécanique. Ce travail de thèse vise à contribuer à la connaissance générale de la rhéologie des zones de cisaillement lithosphérique. Une approche originale a été mise en place, se basant sur l'évolution thermique aux abords et au sein des zones de cisaillement. Sur la base de modèles numériques thermo-cinématiques 2-D et de développements analytiques, la variabilité de premier ordre de l'évolution et de la perturbation thermique est analysée et quantifiée au regard de l'influence des trois processus thermiques majeurs que sont la diffusion, l'advection et le shear heating. Les résultats sont confrontés aux signatures thermiques métamorphiques associées aux chevauchements intra-continentaux pour lesquels les influences des processus d'accrétion et d'érosion sont également examinées. Le cas du Main Central Thrust (Himalaya), associé à une inversion thermique métamorphique bien développée, est pris comme exemple de référence. Nos résultats quantitatifs mettent en avant le rôle crucial du shear heating, notamment de la variabilité de la résistance mécanique des zones de cisaillement. L'accent est mis sur l'importance des paramètres de fluage des roches. L'étude de zones de cisaillement centimétriques développées au sein de la granodiorite du Zillertal (fenêtre des Tauern, Alpes) à la faveur de faibles variations de la composition minéralogique révèle l'extrême sensibilité de la rhéologie des roches ignées représentatives de la croûte continentale. Les conséquences de cette variabilité intense à petite échelle sont finalement discutées au regard des rhéologies classiquement considérées dans les modèles qui s'intéressent aux processus qui régissent la dynamique de la lithosphère. / Shear zones are common structural features in the lithosphere and occur at various scales (from microscopic to lithospheric). At the lithospheric scale, they concentrate most of the relative movements between tectonic plates, and therefore, accommodate a high amount of strain. Consequently, the understanding of both their spatial and temporal mechanical behaviour is crucial for the general knowledge of the lithosphe dynamics. Rheology of rocks, which define their mechanical behaviour, is controlled by physical laws that predict how they deform under some stresses. Temperature plays a major role in the creep-dislocation behaviour, which characterizes the ductile domain (in depth), decreasing efficiently the rock strength. Furthermore, each rock has intrinsic mechanical properties, which depend on its mineralogical composition, texture and internal structures. However, due to the lack of data directly measurable deeper than a few kilometres, the lithosphere rheology, and in particular the continental lithosphere remains subject to drastically different interpretations. The mechanical behaviour of major shear zones is not fully understood, as they are the location of intense changes of both the rock internal nature and major thermal perturbations. Especially, the mechanical energy, converted into heat (shear heating) causes a close interaction between thermal ad mechanical evolutions. This thesis aims to better understand the rheological state of lithospheric scale shear zones. For this purpose, we used an original approach, based on the temperature field evolution around and within such shear zones. From 2D numerical thermo-kinematic models and analytical developments, the first order variability of thermal evolution and perturbation is anal- ysed and quantified with respect to the impact of three major thermal processes, defined as diffusion, advection and shear heating. Results are compared to metamorphic thermal signatures associated to intra-continental thrust zones for which the influence of both accretion and erosion was also investigated. The case of the Main Central Thrust (MCT) in the Himalayas, whose the inverse metamorphic thermal zonation has been extensively studied, was chosen as the main natural analogue. Our quantitative results highlight the crucial role of shear heating, and more particularly of mechanical strength variability within shear zones. We thus emphasise on the importance of rock creep parameters. The study of centimetre-scale shear zones, which developed within the granodiorite of the Zillertal nappe (Tauern window, Tyrol, Alps) thanks to little local variations of the mineralogical composition, reveals the extreme sensitivity of igneous rocks rheology, representative of the continental crust. The consequences of such an intense variability, revealed at small scale are finally discussed with regard to rheologies usually considered in models that focus on processes controlling lithosphere dynamics.

Made available in DSpace on 2014-07-29T15:25:22Z (GMT). No. of bitstreams: 1 Tese Carina-pos defesa.pdf: 485460 bytes, checksum: 2ca505db4ca73a05349dd92fbfc7df1d (MD5) Previous issue date: 2011-03-18 / Montelukast is a potent reversible selective inhibitor of cysteinilleukotrien- 1 receptor, avoiding that these mediators promote the asthmatic response. Its commercialization in Brazil, as a terminated product, is protected by patent up to 2010. Once the active ingredient Montelukast is recent in the pharmaceutical market and there is no methodology description in official compendiums capable to assure the quality of new formulations, the objective of this paper was the pharmaceutics of montelukast film coated tablets, the development and the validation of analytical and bioanalytical methodologies foreseeing the pharmaceutical equivalence and bioequivalence with the reference medication of the market. With this purpose, some physicalchemical parameters were characterized, assay and dissolution methodologies were developed and validated per high performance liquid chromatography with ultraviolet detection (HPLC-UV) for the quantification of montelukast present in 10.0mg film coated tablets. The quantification of montelukast sodium in human plasma was performed using Loratadine as internal standard and high performance liquid chromatography attached to mass detector (HPLC - MS / MS). The active ingredient was extracted from the human plasma using precipitation extraction. The results found for the parameters of specificity, linearity, accuracy, precision, quantification and detection limits and stability in the methodologies validation confirm they were adequate for the objective proposed. The analytical methodologies developed and validated were applied in the pharmaceutics of the tablets for the determination of the formulation similar to the market reference medication Singulair®. This formulation was submitted to stability assays to assure its quality and to allow the performance of pharmaceutical equivalence and bioequivalence with the purpose of registering as a generic medication. / O Montelucaste é um potente inibidor seletivo reversível do receptor cisteinil-leucotrieno-1, evitando que os mediadores provoquem a resposta asmática. Sua comercialização no Brasil, na forma de produto acabado, é protegida por patente até 2010. Uma vez que o fármaco Montelucaste é recente no mercado farmacêutico e não há descrição de metodologia em compêndios oficiais capaz de assegurar a qualidade das novas formulações, o objetivo deste trabalho foi o desenvolvimento farmacotécnico de comprimidos revestidos de montelucaste, desenvolvimento e validação de métodos analítico e bioanalítico visando obtenção de equivalência farmacêutica e bioequivalência com o medicamento referência de mercado. Com esta finalidade, foram caracterizados alguns parâmetros físico-químicos, desenvolvidos e validados métodos de doseamento e dissolução por cromatografia líquida de alta eficiência com detecção ultravioleta (HPLC-UV) para quantificação de montelucaste presente em comprimidos revestidos de 10,0 mg. A determinação de montelucaste sódico em plasma humano foi realizada utilizando-se loratadina como padrão interno e cromatografia líquida de alta eficiência acoplada a detector de massas (HPLC MS/MS). O fármaco foi extraído do plasma humano utilizando extração por precipitação. Os resultados encontrados dos parâmetros de especificidade, linearidade, exatidão, precisão, limites de quantificação e detecção e estabilidade nas validações dos métodos confirmam que os mesmos foram adequados para a finalidade proposta. Os métodos analíticos desenvolvidos e validados foram aplicados no desenvolvimento farmacotécnico dos comprimidos para determinação de uma formulação próxima ao medicamento referência de mercado Singulair®. Esta formulação foi submetida a ensaios de estabilidade para assegurar sua qualidade e permitir a realização de equivalência e bioequivalência farmacêutica com o intuito de registro como medicamento genérico.

La matière organique dissoute (MOD) est constituée d’un mélange hétérogène et complexe de molécules. Elle intervient dans de nombreux processus physiques, biologiques et chimiques dans les milieux aquatiques, et notamment dans les grands cycles biogéochimiques ou le transport et la biodisponibilité des contaminants.Ainsi un des enjeux actuels de nombreux domaines de recherche (chimie, écologie, océanographie) est de mieux comprendre et caractériser la MOD dans l’environnement. Dans ce contexte-là, l’objectif de ces travaux a été le développement d’une méthodologie analytique pour l’analyse et la séparation, en fonction de la taille, par fractionnement par couplage flux-force avec flux asymétrique (AF4) de la MOD. Le développement a principalement porté sur la phase mobile, le flux croisé, le temps de focus et l’utilisation d’étalons organiques proches de la MOD, permettant de calculer sa masse moléculaire moyenne.Cette méthode optimisée, couplée à un détecteur UV/Vis, équipée d’une membrane de 1kDa, d’un espaceur de 490μm et d’une phase mobile de 5mM en tampon phosphate a permis l’étude de la dynamique de la MOD.L’application de cette méthode couplée aux techniques de spectroscopie optique (absorbance et fluorescence) a permis l’étude de la MOD dans les estuaires de Seine et de Gironde mettant en avant les effets de la marée et des saisons sur la taille et le type de MOD.De plus, différentes approches statistiques ont été développées afin de mieux appréhender les multiples variables (analytiques ou environnementales) et notamment les modèles de régression linéaire ou les cartes auto-organisatrices de Kohonen. / Dissolved organic matter (DOM) is a heterogeneous and complex mixture of molecules. It is involved in many physical, biological and chemical processes in aquatic ecosystems, especially in the major biogeochemical cycles or transport and bioavailability of contaminants.Thus one of the current issues in many areas of research (chemistry, ecology, oceanography) is to better understand and characterize DOM in the environment. In this context, the aim of this work was the development of an analytical methodology for DOM analysis and separation, depending on its size, by asymmetrical flow field-flow fractionation (AF4). The development focused on the mobile phase, the cross-flow, the focus time and the use of organic macromolecules standards close to DOM, in order to calculate its molecular weight.This optimized method, coupled with a UV/Vis detector, equipped with a 1kDa membrane, a 490μm spacer and a mobile phase of 5 mM phosphate buffer allowed us to study the MOD dynamics in estuarine environments.The application of this method coupled to optical spectroscopy techniques (absorbance and fluorescence) permitted the study of MOD in the Seine and Gironde estuaries and to highlight the tidal and the seasonal effects on the size and type of DOM.Furthermore, different statistical approaches have been developed to better understand the multiple variables (analytical or environmental), especially linear regression models or self-organizing maps (Kohonen).