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Optimisation de molécules extractantes pour le multi-recyclage du Plutonium dans les combustibles de nouvelle génération. / Extracting molecules optimization for Plutonium multi-recycling in new generation fuels.Berger, Clémence 23 July 2019 (has links)
Ces travaux de thèse, effectués dans le cadre des études sur le retraitement des combustibles nucléaires usés par extraction liquide-liquide, concernent l’évaluation des performances d’extraction d’une nouvelle famille de molécules : les carbamides (R1R2NC(O)NR3R4). Cette famille peu étudiée jusqu’à maintenant apparait comme pertinente pour la séparation chimique de l’uranium et du plutonium à partir d’une solution d’acide nitrique concentrée. Le procédé envisagé permettrait une co extraction de l’uranium et du plutonium à forte concentration d'acide nitrique (4 mol.L 1) ainsi qu’une séparation de ces deux éléments à plus faible concentration d'acide nitrique (0,5 mol.L-1) sans avoir recours à des réactions d’oxydo-réduction comme c’est le cas pour le procédé industriel PUREX actuellement mis en œuvre dans les usines de retraitement de La Hague.En vue de l’optimisation de la structure de ces nouveaux extractants, 17 carbamides ont été étudiés. L’influence de la longueur des chaînes alkyle, du nombre de substituants, du nombre et de la position de ramifications a été évaluée sur l’extraction de l’uranium et du plutonium ainsi que sur la sélectivité U/Pu. Les résultats ont montré que certains carbamides sont des extractants performants vis-à-vis de l’uranium. La présence d’un groupement –NH sur la fonction carbamide améliore l’extraction alors que l’ajout de ramifications sur les chaines alkyles diminue l’extraction ainsi que la séparation U/Pu. Des études complémentaires sur la capacité de charge et la viscosité ont permis d’optimiser la structure et de proposer des candidats répondant aux critères de développement d’un procédé.La spéciation de l’uranium et du plutonium en phase organique en fonction de divers paramètres (structure du carbamide, concentration d'acide nitrique, etc) a mis en évidence les différents complexes formés: UO2(NO3)2L2; UO2(NO3)3(HL) et {UO2(NO3)L2}(NO3)pour l’uranium et Pu(NO3)4L2 et Pu(NO3)6(HL)2 pour le plutonium. Un lien entre les différences de propriétés extractantes et la nature des complexes formés en phase organique a été mis en évidence. En particulier, un changement du mécanisme d’extraction de l’uranium est observé pour les composés portant le groupement –NH. Par ailleurs, l’augmentation de la concentration d’acide nitrique en phase aqueuse favorise fortement la formation des complexes où l’extractant est en sphère externe UO2(NO3)3(HL) et Pu(NO3)6(HL)2 en solution.Enfin la stabilité de ces extractants vis-à-vis de la radiolyse a été étudiée de manière préliminaire. / This thesis, conducted in the framework of the reprocessing of spent nuclear fuels by solvent extraction, concerns the extraction performances evaluation in view of new extractants optimization: carbamide molecules (R1R2NC(O)NR3R4). This extractant family has not attracted much attention in literature but appears as a good substitutes for the chemical separation of uranium and plutonium from an nitric acid aqueous phase. The considering process will allow to extract uranium and plutonium at high nitric acid concentration (CHNO3aq = 4 mol.L-1) and separate these two elements at lower nitric acid concentration (CHNO3aq = 0,5 mol.L-1) without redox chemistry.In these conditions, 17 carbamide extractants were studied to observe the influence of alkyl chains length, substituent number, position and number of (2-ethylhexyl) ramifications on the uranium and plutonium extraction and on the U/Pu selectivity. Results indicate a high uranium extraction by carbamide molecules. Moreover, substituent number have a high influence on the cations extraction whose distribution ratio highly increase with the –NH group presence on the carbamide function. On the other hand, ramifications addition decrease the extraction and the U/Pu separation with the decreasing of distribution ratios. Additional studies on loading capacity and viscosity measurements allow to optimize the structure and some good analogs are proposed to process development.The uranium and plutonium speciation in organic phase as a function of experimental conditions (carbamide structure, nitric acid concentration, etc) allow to highlight formed complexes: UO2(NO3)2L2; UO2(NO3)3(HL) and {UO2(NO3)L2}(NO3) for uranium and Pu(NO3)4L2 and Pu(NO3)6(HL)2 for plutonium. The relation between extracting properties and formed complexes in organic phase has been made. In particular, modification of the uranium extraction mechanism is observed for the compounds containing –NH group. Moreover, the increase of aqueous nitric acid concentration have a favorable effect on the formation of outer sphere complexes UO2(NO3)3(HL) and Pu(NO3)6(HL)2.Then extractant stability of extractant regarding γ radiolysis have also been studied
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Validation and comparison of three sample preparation techniques for quantitation of amobarbital, butalbital and phenobarbital in blood and urine using UFLC-MS/MSChan, Chi Hin 09 October 2019 (has links)
This research study successfully completed three objectives: 1) validate liquid-liquid, supported-liquid, and solid-phase extractions for the quantitation of three barbiturates (amobarbital, butalbital, and phenobarbital) in blood and urine using liquid chromatography-tandem mass spectrometry; 2) to compare the efficiency and effectiveness among methods in accomplishing extraction of barbiturates under the laboratory setting at Boston University School of Medicine; and 3) to report all the analytical data to RTI International for interlaboratory comparison.
For the validation study, a six-point linear calibration model (20-2000 ng/mL) with inversely weighted concentration (1/x) was reproducible in all three sample preparation methods for both blood and urine with r2 greater than or equal to 0.994. Bias and precision evaluated from three controls throughout the range of the curve were within ±20% and ±20%CV, respectively. Neither carryover nor interference was observed. Detection limits were evaluated down to 5 ng/mL depending on the extraction procedure. Samples were able to be diluted up to 50 times prior to instrumental analysis. Samples were stable on autosampler at room temperature up to 72 hours after their initial analysis. Recovery of barbiturates from blood and urine all ranged from 45% to 86%. The effect of ionization suppression or enhancement was found to have minimal impact on the validation.
For choosing the most suitable method quantifying barbiturates, efficiency and effectiveness were studied. Efficiency evaluates the time and ease of sample preparation required to prepare a sample for analysis. Supported-liquid extraction was found to be the most efficient method for extracting barbiturates as it required the least amount of time to perform and could be easily automated with minimal training. Effectiveness is an assessment of one’s ability to selectively recover target analyte at a reasonably low concentration. By considering a method’s recovery, extract cleanliness, detection limits, and reproducibility, liquid-liquid extraction was the best at quantifying barbiturates in blood and supported-liquid extraction was the most suitable method for extracting barbiturates from urine.
For interlaboratory comparison, all the data collected has been reported to RTI International. These findings can be used for examining the overall reliability and reproducibility of the validated methods. Results obtained can also be used to explore the possibility for streamlining sample preparation in the forensic laboratory, and hence reducing the case backlog.
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Evaluation and comparison of various sample preparation techniques for the analysis and quantitation of THC, synthetic cannabinoids, and metabolites by LC-MS/MS in human whole blood and urineBoyle, Sarah 09 October 2019 (has links)
A cannabinoid refers to any natural or synthetic compound that interacts with the CB1 and CB2 receptors. There are currently three different groups of cannabinoids: endogenous cannabinoids, phytocannabinoids and synthetic cannabinoids. The most common phytocannabinoid is delta-9-tetrahydrocannabinol (THC), which is the active component in the Cannabis sativa or marihuana plant1–3. Two examples of synthetic cannabinoids that are present in case reports from 2012 to 2018 are AB-FUBINACA and AB-PINACA4–7.
THC and synthetic cannabinoids are commonly encountered drugs in forensic toxicology cases, therefore, being able to extract these compounds and their metabolites is imperative for toxicological interpretation. There are a variety of commercially available sample preparation techniques for these analytes. Companies such as UCT, Biotage, Millipore-Sigma, Tecan, and Thermo Fisher Scientific manufacture these products. The focus of this research was to evaluate these techniques for their cleanliness, efficiency and cost effectiveness. Sample preparation techniques are designed to remove the different components of the matrix and other prescription or illicit substances present in the sample that could interfere with the assay, increase the analyte recovery, extraction efficiency, decrease variability, and clean-up the sample to allow for less instrument downtime and longer column life8. This study focused on comparing a liquid-liquid extraction (LLE), solid phase extraction (SPE), and supported liquid extraction (SLE).
The primary purpose of this study was to develop and validate the three above mentioned sample preparation techniques for the analysis of THC, 11-hydroxy-THC, 11-nor-9-carboxy-THC (THCCOOH), AB-FUBINACA, AB-FUBINACA metabolite 3, and AB-PINACA in blood and urine.
Parameters assessed followed Academy Standards Board (ASB) Standard 036, Standard Practices for Method Validation in Forensic Toxicology, including recovery, suppression, and matrix effects.
For urine and blood analysis, the calibration range was determined to be 1 ng/mL to 50 ng/mL for all three techniques. Urine recovery was highest for the LLE method, with all compounds having a recovery greater than 50%. The SLE method had the lowest LOQ results for urine, with 0.5 ng/mL for 11-hydroxy-THC and THCCOOH, 0.75 ng/mL for THC, AB-FUBINCA and AB-FUBINACA metabolite 3, and 1 ng/mL for AB-PINACA. Ion suppression was reduced using the SLE method for urine along with having the shortest sample preparation time of 1 hr for up to 48 samples.
For blood analysis, the LLE method had the greatest recovery of all analytes. The LLE method also had reduced suppression and matrix effects compared to the SPE method. Sample preparation was shorter for the SPE method, consuming 2 hrs for an average sample batch, compared to 4 hrs for the LLE method, which included a 2 hr freezing step.
In conclusion, for urine analysis, all three sample preparation techniques were acceptable for the analysis of THC, synthetic cannabinoids, and their metabolites, with the SLE method being the preferred method. For blood analysis a LLE and SPE method were developed and are adequate for the analysis of THC, synthetic cannabinoids, and their metabolites, with the LLE method being the preferred method.
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Comparison of sample preparation techniques on twenty-three drugs in human whole blood and urineMcGowan, Courtney K. 10 October 2019 (has links)
In forensic toxicology, analysis of drugs and metabolites in biological fluids is performed to determine cause of death, suspected drug use, drug facilitated sexual assaults, or whether someone was driving under the influence. Analyte identification and concentration determination can be determined in a variety of matrices (e.g., blood, urine, or oral fluid) and can be complex. It is therefore necessary to have optimal sample preparation and instrumental conditions that work for all matrices of interests. Determining the best approach can be challenging due to the amount of time and resources to perform expansive evaluations of sample preparation, stationary/mobile phases, liquid chromatography (LC) conditions and mass spectrometry (MS) operating parameters.
In this study three different sample preparation methods were validated for blood and urine. The three sample preparation methods were solid-phase extraction (SPE), supported liquid extraction (SLE), and liquid-liquid extraction (LLE). Six different drug groups were used as the analytes being tested by the methods. These drug groups were amphetamines, local anesthetics, opioids, hallucinogens, antidepressants, and novel psychoactive substances (NPS). A total of twenty-three drugs were used: amphetamine, methamphetamine, (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), and 3,4-methylenedioxymethamphetamine (MDMA), benzoylecgonine (BZE), cocaine, lidocaine, codeine, methadone, morphine, 6-monoacetylmorphine (6-MAM), fentanyl, oxycodone, lysergic acid diethylamide (LSD), phencyclidine (PCP), amitriptyline, citalopram, fluoxetine, trazodone, ethylone, α-pyrrolidinopentiophenone (α-PVP), and 25I-NBOMe.
The methods were validated according to guidelines set forth by the Scientific Working Group for Forensic Toxicology (SWGTOX) Standard Practices for Method Validation in Forensic Toxicology and the American Academy of Forensic Science (AAFS) Standards Board (ASB) draft of Standard Practices for Method Validation in Forensic Toxicology. Parameters of calibration model, bias, precision, limit of detection (LOD), limit of quantitation (LOQ), dilution integrity, ion suppression/enhancement, interference studies, and stability were evaluated. Recovery was also assessed to determine the efficiency of the extraction. Calibration models met the 0.98 R2 minimum requirement. For all sample preparations the compounds evaluated in each were found to be stable for at least 72 hours. Interferences were found to be similar across all three sample preparation methods. Parameters of bias, precision, and dilution integrity were largely comparable between all three methods. Overall for LOD, SLE resulted in lower values for blood and urine ranging for 0.1 to 5 ng/mL. Overall for LOQ, SLE resulted in lower values for blood and LLE resulted in lower values for urine in the range of 0.5-10 ng/mL. SLE resulted in the highest recovery for all twenty-three analytes, due to LLE failing to extract consistently or completely for benzoylecgonine, morphine, and 6-monoacetylmorphine. Overall, SLE resulted in the lowest percent values for ion suppression and enhancement for both blood and urine. Overall, blood resulted in high ion suppression (exceeding -20%) for SPE and LLE.
Final determination overall was that SLE was the best sample preparation method for all twenty-three analytes. This was determined based on the evaluation of recovery, ion suppression/enhancement, and LOD, as well as sample preparation time. Sample preparation time for SLE was approximately 1 hour, while SPE took 2.5 hours and LLE 2 hours.
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A study of the adsorption isotherms of Ion-pair reagents / En studie av adsorptions isotermerna hos jonpar reagenserBilici, Mehmet January 2022 (has links)
In this project, the optimization of obtaining adsorption isotherms for the ion pair reagent, tributylamine was tested. The goal was to have a better understanding of the chromatographic process when separating biomolecules, such as oligonucleotides. To do this one ion pair reagent was tested in different buffers with different compositions of acetonitrile. These solutions adsorbed into a C18 column at different temperatures and stripped into fractions of 35 mL. To analyze the results Liquid-liquid extraction was performed on the fractions and the organic phase was then injected into a gas chromatography. The results showed that at a temperature of 24°C the ion pair reagent adsorbed more to the column than at 37°C and 50°C. For the different compositions of acetonitrile buffers which were tested the one that stood out was the 50% acetonitrile buffert. At all temperature it showed to always be able to adsorb more to the column than the other buffers. To calculate the concentrations of the analytes, standard curves for both tributylamine and dibutylamine were made. For dibutylamine, four unknown samples were provided to test out if the methods could be used to determine the concentrations of dibutylamine in the samples. The methods for acquiring adsorption isotherms and analyzing samples with the gas chromatography showed good results and could be used for more studies. However, to validate the results of the 50% acetonitrile buffer, more work in the future is required.
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Advanced Charge-Storage Materials for Supercapacitor ApplicationsSyed, Aseeb January 2019 (has links)
MnO2 continues to gain traction in the research and development of advanced
supercapacitor materials due to its arsenal of advantages, such as high capacitance, low cost,
natural abundance, and environmental benignity. However, its low conductivity has hindered its
adoption into real-life applications. Compositing MnO2 with conductive additives has proved to
be a promising route for the improvement of its power-energy characteristics. Four novel
colloidal techniques were developed for the synthesis of MnO2-CNT composites with enhanced
performance at high active mass loading. One strategy utilized a Schiff-based linkage of
dispersants such as 3,4-Dihydroxybenzaldehyde (DHB) and Toluidine Blue O (TDB) to
effectively mix and disperse MnO2 and CNT. Secondly, a co-dispersion technique was also
investigated using Gallocyanine to improve dispersion and mixing of MnO2 and MWCNT.
Third, a novel liquid-liquid extraction technique opened new avenues in agglomerate-free
processing of individual components, which allowed enhanced electrode performance. Lastly, a
morphology-modification strategy was also undertaken by synthesizing MnO2 nanorods with the
use of advanced organic dispersants to control the aspect ratio and composite nanorods with
MWCNT.
The second major material investigated was polypyrrole (PPy), a polymer material with
high conductivity, ease of synthesis, low-cost, and non-toxicity. However, its low cyclic stability
was prevented it from being applied for real-world applications. Certain anionic and aromatic
dopants have shown to improve the conductivity and cyclic stability. Therefore, one of the
investigations in this work attempted to improve the performance of PPy-CNT composites by
use of a novel anionic dopant, Sunset Yellow (SY). For all investigations electrodes with high mass loadings were produced to achieve high areal capacitance, thus ensuring the practicality of the
techniques / Thesis / Master of Applied Science (MASc) / Supercapacitors (SCs) and batteries are both electrochemical energy storage devices.
While batteries excel at storing energy in high volumes, supercapacitors excel in charging (and
discharging) at extremely high rates. It is desirable to obtain the best of both worlds in a single
device; high energy volume and fast charging speeds. Although such a feat is not out of the
realm of theoretical possibility, current projections forecast supercapacitors to compliment
battery technologies instead of replacing them. Nonetheless, constant progression in the field of
SCs is needed to sustain and proliferate their adoption into emerging markets. Therefore, the aim
of this research was to assist in the endeavours to improve current SC technologies from a
materials science standpoint.
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Development of a liquid-liquid extraction method of resveratrol from cell culture media using solubility parametersAl balkhi, M.H., Mohammad, Mohammad A., Tisserant, L-P., Boitel-Conti, M. 2016 June 1923 (has links)
Yes / The extraction of bioactive compounds, produced by plant cell cultures, directly from their culture medium, which contains other by-products, is a great challenge. Resveratrol extraction from its grapevine cell cultures is considered here as an example to improve the extraction processes from plant cell cultures using solubility parameters. Successive liquid-liquid extraction (LLE) processes were exploited to extract resveratrol from the culture medium with an extraction ratio approaching 100%, high selectivity and minimum amounts of solvents. The calculations of partition coefficients as a function of solubility parameters demonstrated that benzyl benzoate is the most suitable intermediate solvent to extract resveratrol from its aqueous medium. The calculations also illustrated the high ability of methanol and ethanol to extract resveratrol from benzyl benzoate. The physicochemical properties of benzyl benzoate and processing conditions were exploited to separate it from aqueous media and organic solvents. The agitation method, component ratios and extraction time were studied to maximize the extraction yield. Under the best studied conditions, the recovery of resveratrol from different culture media approached ∼100% with a selectivity of ∼92%. Ultimately, the improved extraction processes of resveratrol are markedly efficient, selective, rapid and economical. / Mohammad Amin Mohammad gratefully acknowledges CARA (The Council for At-Risk Academics, Stephen Wordsworth and Ryan Mundy) for providing the financial support for an academic fellowship.
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Modelling and optimisation of oxidative desulphurization process for model sulphur compounds and heavy gas oil : determination of rate of reaction and partition coefficient via pilot plant experiment : modelling of oxidation and solvent extraction processes : heat integration of oxidation process : economic evaluation of the total processKhalfalla, Hamza Abdulmagid January 2009 (has links)
Heightened concerns for cleaner air and increasingly more stringent regulations on sulphur content in transportation fuels will make desulphurization more and more important. The sulphur problem is becoming more serious in general, particularly for diesel fuels as the regulated sulphur content is getting an order of magnitude lower, while the sulphur contents of crude oils are becoming higher. This thesis aimed to develop a desulphurisation process (based on oxidation followed by extraction) with high efficiency, selectivity and minimum energy consumption leading to minimum environmental impact via laboratory batch experiments, mathematical modelling and optimisation. Deep desulphurization of model sulphur compounds (di-n-butyl sulphide, dimethyl sulfoxide and dibenzothiophene) and heavy gas oils (HGO) derived from Libyan crude oil were conducted. A series of batch experiments were carried out using a small reactor operating at various temperatures (40-100 °C) with hydrogen peroxide (H2O2) as oxidant and formic acid (HCOOH) as catalyst. Kinetic models for the oxidation process are then developed based on 'total sulphur approach'. Extraction of unoxidised and oxidised gas oils was also investigated using methanol, dimethylformamide (DMF) and N-methyl pyrolidone (NMP) as solvents. For each solvent, the 'measures' such as: the partition coefficient (KP), effectiveness factor (Kf) and extractor factor (Ef) are used to select the best/effective solvent and to find the effective heavy gas oil/solvent ratios. A CSTR model is then developed for the process for evaluating viability of the large scale operation. It is noted that while the energy consumption and recovery issues could be ignored for batch experiments these could not be ignored for large scale operation. Large amount of heating is necessary even to carry out the reaction at 30-40 °C, the recovery of which is very important for maximising the profitability of operation and also to minimise environmental impact by reducing net CO2 release. Here the heat integration of the oxidation process is considered to recover most of the external energy input. However, this leads to putting a number of heat exchangers in the oxidation process requiring capital investment. Optimisation problem is formulated using gPROMS modelling tool to optimise some of the design and operating parameters (such as reaction temperature, residence time and splitter ratio) of integrated process while minimising an objective function which is a coupled function of capital and operating costs involving design and operating parameters. Two cases are studied: where (i) HGO and catalyst are fed as one feed stream and (ii) HGO and catalyst are treated as two feed streams. A liquid-liquid extraction model is then developed for the extraction of sulphur compounds from the oxidised heavy gas oil. With the experimentally determined KP multi stage liquid-liquid extraction process is modelled using gPROMS software and the process is simulated for three different solvents at different oil/solvent ratios to select the best solvent, and to obtain the best heavy gas oil to solvent ratio and number of extraction stages to reduce the sulphur content to less than 10 ppm. Finally, an integrated oxidation and extraction steps of ODS process is developed based on the batch experiments and modelling. The recovery of oxidant, catalyst and solvent are considered and preliminary economic analysis for the integrated ODS process is presented.
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Extraction liquide-liquide sur matériaux poreux. Mise en oeuvre et recherche de paramètres influents.Porhel, Sabine 02 April 2013 (has links)
Cette étude s'inscrit dans la problématique de l'extraction minière de l'uranium. L'étape plus spécifiquement visée est celle de l'extraction liquide-liquide au cours de laquelle l'uranium en solution aqueuse de lixiviation est transféré dans une phase organique par une complexation avec une amine tertiaire (Alamine 336®). L'étude porte sur cette étape de séparation par le biais d'un contact liquide-liquide sans dispersion assuré au travers d'une membrane macroporeuse organique (pertraction). Cette technologie permet l'utilisation de phases de densités proches. Ainsi, l'extraction de l'uranium et du molybdène, co-extrait industriellement par l'Alamine 336, ont été étudiées pour différentes concentrations élevées en molécules extractantes. Pour cela, l'ensemble des paramètres physico-chimiques influents du système chimique (courbe de distribution, viscosité, densité, tension de surface, coefficient de diffusion à l'infini, etc.) et de la membrane (porosité, dimensions, tortuosité, etc.) sont caractérisés. Des essais de pertraction sur un dispositif unitaire de fibre creuse, développé dans le cadre de cette étude, sont réalisés et les résultats sont modélisés par une approche de résistances du transfert de matière en séries. Un seul paramètre ajustable est retenu : le coefficient de diffusion en phase organique. Cette modélisation permet de mettre en évidence les limitations au transfert de l'uranium de la phase aqueuse vers la phase organique lors du processus d'extraction à travers la membrane liées au système chimique, aux débits et à la membrane. / This study is falls within the framework of uranium mining. The step more specifically aimed is the solvent extraction during which the uranium is transferred from a lixiviation aqueous solution to an organic phase by a complexation with a tertiary amine (Alamine 336®). The study focuses on this step of separation using a liquid-liquid contact without dispersal guaranteed by an organic macroporous membrane (pertraction). This technology allows the use of phases with close densities. So, uranium and molybdenum extraction, co-extracted industrially by Alamine 336, were studied for various high extractantes molecules concentrations. For that purpose, all the influential physical chemical parameters of the chemical system (distribution curve, viscosity, density, surface tension, infinite diffusion coefficient, etc.) and of the membrane (porosity, size, tortuosity, etc.) are characterized. Pertraction essays on a single hollow fibre, developed within the framework of this study, are performed and the results are modelized by an approach of mass transfer resistances in series. A single adjustable parameter is retained: the diffusion coefficient in organic phase. This modelling allows highlighting the limitations of uranium transfer from the aqueous phase towards the organic phase during the extraction process through the membrane function of chemical system, the flows and the membrane.
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Análise do mesilato de imatinibe em plasma empregando a eletroforese capilar / Determination of imatinib mesylate in plasma by capillary electrophoresisTatiana Okura Ajimura 22 November 2010 (has links)
O mesilato de imatinibe é um importante fármaco pertencente à classe dos inibidores da tirosina-quinase, desenvolvido e utilizado atualmente no tratamento da Leucemia Mielóide Crônica. No histórico da utilização deste medicamento, casos de resistência tem sido relatados cujos mecanismos envolvidos, além dos mecanismos celulares, podem estar relacionados ao metabolismo aumentado deste fármaco. O imatinibe é metabolizado principalmente pelo CYP 3A4, cuja atividade enzimática apresenta grande variabilidade interindividual e é suscetível a indução ou inibição por inúmeras co-medicações, constituintes ambientais e dietéticos. Sendo assim uma dose do medicamento pode resultar em concentrações plasmáticas muito diferentes entre pacientes. A maior parte dos métodos existentes para a determinação do imatinibe em amostras biológicas utiliza a cromatografia líquida de alta eficiência. Entretanto, o método desenvolvido e validado neste trabalho propôs a utilização da eletroforese capilar para a análise deste fármaco em plasma. Para isto foi utilizado um capilar de sílica fundida (46,5 cm de comprimento total, 38 cm de comprimento efetivo e 50 µm de diâmetro interno), tampão fosfato de sódio 50 mmol/L, pH 2,5 como eletrólito de corrida, injeção hidrodinâmica por 20 s a pressão de 50 mbar, tensão de 30 kV, temperatura de 35 °C e detecção em 200 nm. O procedimento de preparo das amostras foi baseado na extração líquido-líquido com o éter metil-terc-butílico como solvente extrator. Os parâmetros de desempenho analítico, linearidade, precisão, exatidão, recuperação, limite de quantificação, seletividade e estabilidade, avaliados na validação do método, cumpriram os requisitos preconizados na legislação vigente e o método desenvolvido foi validado com sucesso. Além disso, sua aplicação foi demonstrada na análise de amostras de plasma de pacientes portadores de Leucemia Mielóide Crônica. / Imatinib mesylate is an important tyrosine kinase inhibitor that has been used for the treatment of Chronic Myeloid Leukemia (CML). Despite the efficacy of imatinib therap, some cases of treatment resistance have been described. A number of mechanisms of resistance have been identified, which include innate or acquired mutations in the BCR-ABL gene, imatinib binding to 1- acid glycoprotein and altered imatinib pharmacokinetics. Imatinib is mainly metabolized by CYP 3A4, whose enzymatic activity presents a large inter-individual variability and is susceptible to induction or inhibition by numerous co-medications, environmental and dietary constituents. Therefore a given dose can yield very different circulating concentrations between patients. The major of methods available for the determination of imatinib in biological samples apply high performance liquid chromatography as analytical technique. However, in this work, we developed and validated a method by capillary electrophoresis for the determination of this drug in human plasma. The analysis was performed using a fused silica capillary (50 µm internal diameter x 46.5 cm total length, 38.0 cm effective length), a 50 mmol/L sodium phosphate buffer pH 2,5 as background electrolyte, hydrodynamic injection time of 20s (50 mbar), voltage of 30 kV, capillary temperature of 35°C and detection at 200 nm. Plasma samples pre-treatment involved liquid-liquid extraction with methyl-terc-butyl ether as extractor solvent. The analytical parameters investigated, linearity, precision, accuracy, recovery, limit of quantification, selectivity and stability, presented in accordance with the confidence criteria established in the literature. Furthermore the application of the method was performed in the analysis of plasma samples from CML patients undergoing treatment with imatinib.
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