No description available.

The purpose of this study was to design a dosing regimen and evaluate the safety of zonisamide (ZNS) following multiple dosing and to determine appropriate monitoring methods. Clinical pharmacokinetics were studied in 8 adult dogs (4 male and 4 female) ranging from 3 to 4 years of age using a randomized crossover design following single intravenous (IV) and oral administration, 6.85 and 10.25 mg/kg, respectively. Samples were collected intermittently for 48 hours. Dogs were then dosed orally (10.17 mg/kg) twice daily for 8 weeks. Blood samples were collected weekly and at discontinuation of the drug. Additionally, urine was collected to determine 24 hour urine ZNS clearance following IV administration. Safety was based on clinical pathology, thyroid and urine testing during both studies. ZNS was measured using high performance liquid chromatography in serum, plasma, erythrocytes (RBC) and whole blood. Data were subjected to standard non-compartmental pharmacokinetic analysis using computer assisted linear regression (WinNonLin?). Comparisons were made in different compartments using one-way ANOVA to identify any differences. Safety parameters at study beginning and end were compared using a Student t-test. ZNS concentrations differed among blood compartments after single dosing, with oral maximum concentration (Cmax) being greatest in RBC (28.73?g/ml) and least (14.36?g/ml) in plasma. Volume of distribution also differed, being greater (1096.05ml/kg) in plasma and least in (379.23ml/kg) RBC. Clearance of ZNS was 57.55ml/hr/kg from plasma and 5.06ml/hr/kg from RBC. Elimination half- life in plasma was 16.4 hr in serum and 57.4 hr in RBC. Bioavailability was 126.8% for RBC and 189.6% for plasma. Following multiple dosing, at steady-state, Cmax averaged 65.8?g/ml with fluctuations of 17.2% between dosings. Accumulation of ZNS was 3.5 (plasma) and 4.3 (RBC). Concentrations did not differ among blood compartments at the end of multiple dosing. Although differences did occur across time in clinical pathology tests, all were within normal limits at study end except for T4. In conclusion, ZNS dosed at 10 mg/kg twice daily for dogs would maintain therapeutic levels (10 to 70?g/ml) recommended in human epileptic patients. Therapeutic monitoring would be best measured in serum or plasma accompanied with thyroid and urine testing.

No description available.

No description available.

Il est maintenant avéré que les contaminants présents dans les milieux aquatiques peuvent être toxiques à l’état de traces voire d’ultra traces. Il est donc important de développer des méthodes d’analyse performantes et sensibles pouvant atteindre ces niveaux de concentration. Dans cette optique, les techniques chromatographiques couplées à la spectrométrie de masse (GC-MS et LC-MS/MS) sont généralement utilisées pour l’analyse des polluants organiques. Les composés présents dans les milieux aquatiques possèdent des propriétés physico-chimiques très variées, d’apolaires à très polaires. Ainsi, développer une analyse simultanée pour toutes ces molécules représente un challenge analytique. Dans ce travail de thèse, plusieurs étapes du processus analytique ont été évaluées : la préparation de l’échantillon par extraction sur phase solide (SPE), la séparation par chromatographie et la détection par spectrométrie de masse. Une liste de composés modèles couramment retrouvés dans les milieux aquatiques a été établie pour conduire ces essais. Les méthodes d’extraction en phase solide hors ligne et en ligne ont été développées dans une optique d’analyse multirésidus à un niveau de traces. Les méthodes chromatographiques, gazeuse et liquide, couplées à la spectrométrie de masse ont été étudiées pour favoriser une analyse exhaustive et sensible. La dernière partie a consisté à appliquer les méthodes développées pour une approche d’analyse non ciblée. / It is now widely recognized that contaminants present in aquatic environments can be toxic at traces or even ultra-traces level. Therefore, it is important to develop efficient and sensitive analytical methods to reach these levels of concentration. In that respect, chromatographic techniques coupled to mass spectrometry (GC-MS and LC-MS / MS) are commonly used for the analysis of organic pollutants. The substances encountered in aquatic environments display a large range of physico-chemical properties, from apolar to very polar. Thus, developing a simultaneous analysis for all these molecules represents an analytical challenge. In this pHD work, several steps of the analytical process have been investigated: sample preparation by solid phase extraction (SPE), chromatographic separation and the detection by mass spectrometry. A list of model compounds commonly determined in aquatic environments was established to conduct the tests. Solid phase extraction methods, offline and online, were developed in a multiresidue analysis aim at traces level. Chromatographic methods, gaseous and liquid, coupled to mass spectrometry were studied to obtain an exhaustive and sensitive analysis. The last part consisted to apply the developed methods for a non-targeted analysis approach.

>Magister Scientiae - MSc / The objective of the thesis is to develop highly efficient catalysts for solid polymer electrolyte (SPE) electrolyser anodes.The anode is the primary cause of the large overpotential of SPE electrolysers and also adds significantly to the cost of the electrolysers. Currently, unsupported IrO2 is a widely used anode catalyst as it exhibits the best stability during the oxygen evolution reaction. The activity of IrO2 needs to be improved significantly to address the high cost and efficiency issues of the SPE electrolyser. Developments aimed at improving the activity of unsupported IrO2 are however limited due to the limitations of the wellknown supports under the operating conditions of electrolysers, leading to their oxidation.In this study binary metal oxides based on IrO2 were developed and optimized as anode catalysts for the SPE electrolyser and compared to the ‘state-of-art’ commercial IrO2 catalyst. The Adams fusion method was adapted and used to synthesize the catalysts.The activities of the catalysts were determined using half-cell studies. Optimum conditions for the preparation of unsupported IrO2 catalysts were found to be 350 oC and 2 hours. The resulting catalysts had twice the activity of the ‘state-of-art’ commercial IrO2 catalyst. Secondary metals were carefully selected, after carrying out both a literature study and an experimental study. Binary metal oxides were then developed using the optimum synthesis conditions. Four binary metal oxides were studied to identify the best/most efficient catalyst for electrolysis. The catalysts were characterized using XRD, TEM, SEM and EDS analyses, in efforts to understand and correlate the activity of the catalysts to its physical properties and obtain information that could be useful for the further development of efficient catalysts.Although all the binary metal oxides studied showed improved activity compared to IrO2, the catalytic activity of Ir0.7Ru0.3O2 was found to be significantly better than the commercial catalyst: it was over 5 times more active than the ‘state-of-art’ commercial IrO2 catalyst. Ir-Pd mixed oxides also proved to be highly efficient as anode catalysts for SPE electrolysers.

This diploma thesis addresses the presence and determination of chloramphenicol residues in biological materials. The theoretical part presents the literature retrieval containing information about veterinary medicaments with the banned use in food producing animals and also the sum of the legislative requirements concerning the presence of these substances in foodproducts and raw food materials of animal origin. The comparison was carried out between the existing analytical methods used for the determination of chloramphenicol residues in different biological materials, which are altogether based on the solid phase extraction for the extract cleaning and the new procedures for sample preparations using columns where the sorbent performs on the molecularly imprinted polymers principle.

The work has been focused on the preconcentration techniques for determination of uranium on the modified sorbent, with the final use of ICP-OES and ICP-MS. First ICP-OES at a wavelength of 385.958 nm was used for determination of uranium. Parameters were optimized and the effect of mineral acids (HCl, HNO3), tensides (Septonex, Ajatin) and organic reagents like (4-(2-pyridylazo)resorcinol, ammonium pyrrolidinedithiocarbamate, 8-hydroxyquinoline-5-sulphonic acid and 1,2-dihydroxyanthraquinone-3-sulphonic acid) was observed. For ICP-MS an isotope 238U was chosen. As an internal standard 209Bi (200 ?g•l-1) was used. Modified silica gel was used (Silicagel tethered with C18, C8 alkyls and phenyl) and two types of Amberlite XAD 4 and XAD 16 for the preconcentration of uranium (VI). Commercially produced Amberlite was modified as follows: Drying at 100 °C (24 hours), milled, minced sorbent was selected and fractionated to particles size ranging from 0.32 to 0.63 ?m and finally activated in methanol. The deionised water and Septonex (5•10-3 mol•l-1) at pH 8 were used for Amberlite conditioning. The optimal sorption of uranium (VI) proceeded at pH 8 in the presence of 4-(2-pyridylazo)resorcinol or ammonium pyrrolidinedithiocarbamate with Amberlite XAD-16 moreover with 1,2-dihydroxyanthraquinone-3-sulphonic acid. All organic reagents have mass concentration five time larger than uranium . For the elution of uranium the mixture of 1 mol•l-1 HNO3 with acetone (ratio of 1:1) was used. Acetone was evaporated and the final analysis performed using ICP-OES. The preconcentration of uranium (VI) using Silicagel-C18 conditioning was performed with ethanol, deionised water and Zephyraminu (5•10-4 mol•l-1) at pH 8. For the Silica-C8 and Silicagel-Phenyl the same conditioning procedure without zephyramin was used. Silica-C18 had the highest sorption efficiency with 1,2-dihydroxyanthraquinone-3-sulphonic acid, Silicagel-C8 with ammonium pyrrolidinedithiocarbamate and Silicagel-Phenyl with 8-hydroxyquinoline-5-sulfonic acid, all organic reagents have mass concentration five time larger than uranium concentration. As an optimal elution mixture acetone and ethanol (ratio of 1:1) in the presence of 1 mol•l-1 HCl was evaluated. Acetone and ethanol was evaporated and the final analysis was performed using ICP-MS. Silicagel-C18 was evaluate as the most effective in the presence of zephyramin and 1,2-dihydroxyanthraquinone-3-sulphonic acid. Sorption was also tested in the presence of 20 ?g•l-1 microelements (Be, V, Co, Ni, Y, Pb, Th, Cd) and in the presence of a defined concentrations of K, Na, Ca, Mg, Al and Fe. Direct analysis of uranium was carried out on samples of water from the river Ploucnice and Turonian aquifers containing uranium, 3,5 and 19,3 ?g•l-1. Different type of water required preconcentration of uranium (VI) on Silica-C18 in the presence of 1,2-dihydroxyanthraquinone-3-sulphonic acid and zephyramin. The analysis results gave statistically satisfactory results, which were confirmed using standard addition of 20 ?g•l-1.

The aim of the thesis is determination and optimization of organic acids in beers using the methods of capillary isotachophoresis (CITP) and high performance liquid chromatography with diode array detection (HPLC/UV). Beer is a complicated matrix therefore the samples need pretreatment using solid phase extraction (SPE). The diploma thesis discusses the optimization of the analytical methods (HPLC/UV and CITP) and optimization of SPE. In the theoretical part, history, characterization and technology of beer production are presented. Further, characteristics of organic acids and methods for organic acid determination are also discussed. The experimental part deals with the preparation of solutions, tested samples, calibration samples. Parameters and procedures of analytical methods (HPLC/UV and CITP) and pretreatment using the solid phase extraction are also described in the experimental part. All results are summarized and compared with the current literature in discussion and conclusion. Eleven beer samples from the retail stores were analyzed. In all samples, six organic acids (lactic, oxalic, succinic, acetic, citric, benzoic) were determined by CITP and five organic acids (lactic, oxalic, succinic, acetic, citric) by HPLC/UV were determined. Results of this study give an overview of the organic acid contents in beer samples.

Residuos de fármacos estão presentes em diversas matrizes ambientais e estudos focados na determinação destes tem ganhado grande importância nos últimos anos, devido ao aumento do consumo de medicamentos pela população. A questão do controle de resíduos de compostos farmacologicamente ativos no meio ambiente aquático foi reconhecida como uma das questões emergentes na Química Ambiental, e tem-se dado maior importância visto que os fármacos são encontrados em matrizes em estudos em concentrações de μgL-1 e ngL-1. Nesta pesquisa estudou-se três fármacos antiflamatórios que são amplamente consumidos pela população: diclofenaco, nimesulida e paracetamol. O método analítico foi desenvolvido e validado para a determinação destes fármacos em amostras de águas superficiais da cidade de São Carlos (SP). Inicialmente foi feita a validação do método proposto segundo a Resolução DOQ-CGCRE-008 do INMETRO. Os limites de detecção, e de quantificação e inferior de quantificação do método para a determinação do diclofenaco, nimesulida e paracetamol, foram, respectivamente, 0,5; 1,1 e 1,1 μgL-1. A linearidade, desvio-padrão relativo, exatidão e recuperação média para o diclofenaco foram, respectivamente, R de 0,99, 3,03%, 100,55% e 97,94%. Para a nimesulida, os valores de linearidade, desvio-padrão relativo, exatidão e recuperação, foram, R de 0,98, 2,43%, 101,46% e 100,67%. Já para o paracetamol obteve-se os seguintes valores para linearidade, desvio-padrão relativo, exatidão e recuperação, R de 0,99, 3,50%, 97,94% e 93,17%, respectivamente. Na segunda etapa deste estudo aplicou-se o método validado na análise de amostras de águas coletadas na cidade de São Carlos (SP). Para o método de extração utilizou-se a extração em fase sólida (SPE) e como técnica analítica utilizou-se o HPLC/DAD. Os resultados não indicaram a presença dos fármacos diclofenaco, nimesulida e paracetamol até o limite de detecção do método empregado. / Residues of drugs are present in various environmental matrices and studies focused on the determination of these have gained in importance in recent years, due to increased drug consumption by the population. The issue of control of residues of pharmacologically active compounds in the aquatic environment was recognized as one of the emerging issues in environmental chemistry, and has given greater importance since the drugs are found in studies in matrices at concentrations μgL-1 and ngL-1. In this study was studied three drugs that are widely consumed by the population: diclofenac, nimesulide and acetaminophen. The analytical method was developed for the determination of these drugs in surface water samples from São Carlos (SP). Initially, made a validation of the method proposed second resolution DOQ-008-CGCRE INMETRO. The detection, quantification and lower quantification limits of method for determining of diclofenac, nimesulide and paracetamol were 0.5, 1.1 and 1.1 μgL-1, respectively. The linearity, relative standard , accuracy and average recovery of the method for diclofenac were, respectively, R equal to 0.99, 3.03%, 100.55% and 97.94%. For nimesulide, the values of linearity, relative standard, accuracy and recovery were R equal to 0.98, and 2.43%, 101.46% and 100.67%. For acetaminophen obtained the following values for linearity, relative standard, accuracy and recovery, R equal to 0.99, 3.50%, 97.94% and 93.17% respectively. In the second stage of the study applied the validated method in the analysis of water samples collected in the São Carlos (SP). For extracting the drugs, SPE cartridges were used followed by HPLC / DAD. The results indicate the absense of the studied drugs diclofenac, nimesulide and acetaminophen down to the detection limits of the method employed.