<p>Studies have been performed to evaluate the use of micellar electrokinetic chromatography (MEKC), one mode of capillary electrophoresis (CE), as an analytical technique in industrial pharmaceutical analysis. The potential for using chemometrics for the optimisation of MEKC methods has also been studied as well as the possibilities of coupling MEKC with mass spectrometry (MS). </p><p>Two methods were developed, one for the determination of ibuprofen and codeine and another for pilocarpine, together with their degradation products and impurities in both cases. MEKC was found to be the most suitable mode of CE for the methods. Both methods were optimised by means of experimental design. Valuable information was gathered and optimum conditions were defined which resulted in fast systems with baseline-separated peaks. The ibuprofen-codeine method was validated according to the recommended validation procedures of the International Conference of Harmonisation. The validation was performed on a commercially available tablet formulation to verify the suitability of the method, i.e. for quantification of the two main compounds and to determine the degradation products and impurities in area% of each main peak. The following parameters were determined: selectivity, linearity, accuracy, precision, detection limit, quantitation limit, robustness and range. The results confirm that the method is highly suitable for its intended purpose, i.e. as a routine method for assay and impurity determination. The MEKC method for ibuprofen-codeine was coupled to a mass spectrometer in order to evaluate the potential of partial filling (PF)-MEKC-MS for identification of impurities in pharmaceutical substances and products. The so-called partial-filling technique was used to prevent the non-volatile micelles from entering the MS and was shown to fulfil its purpose of providing detection limits of about 10 pg. </p><p>The study clearly shows that micellar electrokinetic chromatography is well-suited as an analytical technique in industrial pharmaceutical analysis. </p>

<p>Statistical experimental designs have been used for method development and optimisation of separation. Two reversed phase HPLC methods were optimised. Parameters such as the pH, the amount of tetrabutylammonium (TBA; co-ion) and the gradient slope (acetonitrile) were investigated and optimised for separation of erythromycin A and eight related compounds. In the second method, a statistical experimental design was used, where the amounts of acetonitrile and octane sulphonate (OSA; counter ion) and the buffer concentration were studied, and generation of an α-plot with chromatogram simulations optimised the separation of six analytes.</p><p>The partial filling technique was used in capillary electrophoresis to introduce the chiral selector Cel7A. The effect of the pH, the ionic strength and the amount of acetonitrile on the separation and the peak shape of R- and S-propranolol were investigated.</p><p>Microemulsion electrokinetic chromatography (MEEKC) is a technique similar to micellar electrokinetic chromatography (MEKC), except that the microemulsion has a core of tiny droplets of oil inside the micelles. A large number of factors can be varied when using this technique. A screening design using the amounts of sodium dodecyl sulphate (SDS), Brij 35, 1-butanol and 2-propanol, the buffer concentration and the temperature as factors revealed that the amounts of SDS and 2-propanol were the most important factors for migration time and selectivity manipulation of eight different compounds varying in charge and hydrophobicity. SDS and 2-propanol in the MEEKC method were further investigated in a three-level full factorial design analysing 29 different compounds sorted into five different groups. Different optimisation strategies were evaluated such as generating response surface plots of the selectivity/resolution of the most critical pair of peaks, employing chromatographic functions, simplex optimisation in MODDE and 3D resolution maps in DryLab™.</p><p>Molecular descriptors were fitted in a PLS model to retention data from the three-level full factorial design of the MEEKC system. Two different test sets were used to study the predictive ability of the training set. It was concluded that 86 – 89% of the retention data could be predicted correctly for new molecules (80 – 120% of the experimental values) with different settings of SDS and 2-propanol.</p><p>Statistical experimental designs and chemometrics are valuable tools for the development and optimisation of analytical methods. The same chemometric strategies can be employed for all types of separation techniques.</p>

Studies have been performed to evaluate the use of micellar electrokinetic chromatography (MEKC), one mode of capillary electrophoresis (CE), as an analytical technique in industrial pharmaceutical analysis. The potential for using chemometrics for the optimisation of MEKC methods has also been studied as well as the possibilities of coupling MEKC with mass spectrometry (MS). Two methods were developed, one for the determination of ibuprofen and codeine and another for pilocarpine, together with their degradation products and impurities in both cases. MEKC was found to be the most suitable mode of CE for the methods. Both methods were optimised by means of experimental design. Valuable information was gathered and optimum conditions were defined which resulted in fast systems with baseline-separated peaks. The ibuprofen-codeine method was validated according to the recommended validation procedures of the International Conference of Harmonisation. The validation was performed on a commercially available tablet formulation to verify the suitability of the method, i.e. for quantification of the two main compounds and to determine the degradation products and impurities in area% of each main peak. The following parameters were determined: selectivity, linearity, accuracy, precision, detection limit, quantitation limit, robustness and range. The results confirm that the method is highly suitable for its intended purpose, i.e. as a routine method for assay and impurity determination. The MEKC method for ibuprofen-codeine was coupled to a mass spectrometer in order to evaluate the potential of partial filling (PF)-MEKC-MS for identification of impurities in pharmaceutical substances and products. The so-called partial-filling technique was used to prevent the non-volatile micelles from entering the MS and was shown to fulfil its purpose of providing detection limits of about 10 pg. The study clearly shows that micellar electrokinetic chromatography is well-suited as an analytical technique in industrial pharmaceutical analysis.

Statistical experimental designs have been used for method development and optimisation of separation. Two reversed phase HPLC methods were optimised. Parameters such as the pH, the amount of tetrabutylammonium (TBA; co-ion) and the gradient slope (acetonitrile) were investigated and optimised for separation of erythromycin A and eight related compounds. In the second method, a statistical experimental design was used, where the amounts of acetonitrile and octane sulphonate (OSA; counter ion) and the buffer concentration were studied, and generation of an α-plot with chromatogram simulations optimised the separation of six analytes. The partial filling technique was used in capillary electrophoresis to introduce the chiral selector Cel7A. The effect of the pH, the ionic strength and the amount of acetonitrile on the separation and the peak shape of R- and S-propranolol were investigated. Microemulsion electrokinetic chromatography (MEEKC) is a technique similar to micellar electrokinetic chromatography (MEKC), except that the microemulsion has a core of tiny droplets of oil inside the micelles. A large number of factors can be varied when using this technique. A screening design using the amounts of sodium dodecyl sulphate (SDS), Brij 35, 1-butanol and 2-propanol, the buffer concentration and the temperature as factors revealed that the amounts of SDS and 2-propanol were the most important factors for migration time and selectivity manipulation of eight different compounds varying in charge and hydrophobicity. SDS and 2-propanol in the MEEKC method were further investigated in a three-level full factorial design analysing 29 different compounds sorted into five different groups. Different optimisation strategies were evaluated such as generating response surface plots of the selectivity/resolution of the most critical pair of peaks, employing chromatographic functions, simplex optimisation in MODDE and 3D resolution maps in DryLab™. Molecular descriptors were fitted in a PLS model to retention data from the three-level full factorial design of the MEEKC system. Two different test sets were used to study the predictive ability of the training set. It was concluded that 86 – 89% of the retention data could be predicted correctly for new molecules (80 – 120% of the experimental values) with different settings of SDS and 2-propanol. Statistical experimental designs and chemometrics are valuable tools for the development and optimisation of analytical methods. The same chemometric strategies can be employed for all types of separation techniques.

Terpenos são os principais constituintes dos óleos essenciais e vêm sendo explorados há mais de 3500 anos pela humanidade. Por conta das suas propriedades flavorizantes, são amplamente empregados na indústria de cosméticos e perfumaria. Apresentam ainda uma infinidade de funções biológicas, como promoção de polinização nas plantas, e proteção contra pragas e animais. Além dessas funções, muitos compostos possuem ainda atividade antimicrobiana, anti-inflamatória, antifúngica, entre outras. Tendo em vista a simplicidade estrutural dos terpenos e a alta hidrofobicidade que sugere fracas interações intermoleculares, é difícil de se imaginar como esses compostos conseguem desempenhar funções tão específicas e diversas. É de se esperar que quanto mais complexa a estrutura do composto, mais fácil seja seu reconhecimento pelo organismo. Isso mostra o grande poder de reconhecimento do meio biológico. Nesse trabalho, os parâmetros termodinâmicos de transferência da fase aquosa para a fase micelar de 10 terpenos (carvona, cânfora, cumeno, t-anetol, eugenol, limoneno, citronelal, linalol, terpineol e verbenona) e cumarina em dois sistemas, SDS 30 mmol.kg-1 + TBS 20 mmol.kg-1 e SDS 30 mmol.kg-1 + TBS 20 mmol.kg-1 + 10% v/v de etanol foram determinados buscando elucidar a incorporação micelar desses compostos. Micelas apresentam compartimentos com diferentes polaridades e podem servir como modelo para mimetizar as diferentes interações no meio biológico. Dessa forma, a utilização da cromatografia eletrocinética micelar (MEKC, do inglês Micellar Electrokinetic Chromatography) na determinação dos coeficientes de partição e dos parâmetros termodinâmicos de transferência entre as fases aquosa e micelar desses solutos pode contribuir para o entendimento da distribuição bem como auxiliar na compreensão das funções que os mesmos desempenham na natureza. A hipótese de que os parâmetros termodinâmicos podem elucidar detalhes da incorporação micelar foi ainda testada através da busca de relações lineares de energia de solvatação (LSER, do inglês Linear Solvation Energy Relashionships) com o intuito de evidenciar as principais características moleculares que contribuem para o processo detransferência. Os modelos LSER foram estudados através de regressão múltipla e análises multivariadas de PLS, SPLS, PLS-DA e SPLS-DA, com o objetivo de verificar as propriedades dos terpenos que explicam sua incorporação nas micelas. Outras análises estatísticas multivariadas, como análise de agrupamentos e PCA, foram utilizadas para estudar a variabilidade estrutural dos compostos selecionados, bem como, determinar se os descritores teóricos calculados conseguem descrever as características estruturais dos terpenos. O estudo da termodinâmica de transferência de solutos neutros da fase aquosa para a fase micelar demonstrou que mesmo pequenas diferenças estruturais das moléculas contêm informação sobre a distribuição dos compostos nos compartimentos micelares. Também podese inferir sobre o efeito do etanol nas partições e sobre a própria estrutura micelar. Os resultados para o limoneno mostraram a complexidade envolvida nas partições, levando a ideia de restrição de volume nas micelas modificadas por álcool. Resultados de LSER mostraram que a transferência da fase aquosa para a fase micelar desses compostos é governada principalmente pela interação hidrofóbica onde Vx (Volume de McGowan) foi selecionado como um dos descritores mais importantes para explicar lnP. A análise comparativa dos resultados obtidos pelos dois métodos (estudo dos parâmetros termodinâmicos e LSER) indicou similaridade de resultados. Isso demonstra a grande confiabilidade dos resultados e, então, que estudos similares usando outras soluções micelares e outras classes de compostos (hormônios, flavonoides, aminas, etc.) podem ser muito promissores. / Terpenes are the main constituents of essential oils and have been explored for more than 3,500 years. Because of their flavoring properties, terpenes are widely used in the cosmetics and perfumery industry. They also exert a multitude of ecological functions, such as the promotion of plant pollination and protection against pests and animals. In addition, many compounds have antimicrobial, antifungal, anti-inflammatory activities and others. Given the structural simplicity of terpenes and the high hydrophobicity that suggests weak intermolecular interactions, it is difficult to imagine how these compounds can perform such specific and diverse functions. It is expected that the more complex the structure of the compound, the easier it is its recognition by the organism, which does not seem to be true for this class showing the great power of recognition of the biological system. In this work, the thermodynamic parameters of aqueous and micellar phase transfer of ten terpenes (carvone, camphor, cumene, t-anethol, eugenol, limonene, citronellal, linalool, terpineol, and verbenone) and coumarin in two systems, 30 mmol.kg-1 of SDS + 20 mmol.kg-1 of TBS and 30 mmol.kg-1 of SDS, 20 mmol.kg-1 of TBS, and 10% v/v of ethanol were determined to elucidate the micellar distribution of these compounds. Micelles have compartments that possess different polarities and might be a model to mimic the different interactions that terpenes may have in the biological environment. Thus, the use of micellar electrokinetic chromatography (MEKC) in the determination of the partition coefficients and the thermodynamic parameters of transfer of the aqueous phase to the micellar phase of these solutes can contribute to the understanding of the distribution, as well as help in the understanding of the functions they perform in nature. The hypothesis that the thermodynamic parameters can elucidate details of the micellar incorporation was further analyzed through the search of Linear Solvation Energy Relashionships (LSER), in order to highlight the main molecular characteristics that contribute to the transfer process. The LSER models were studied through multiple regression and other multivariate analyzes, such as PLS, SPLS, PLS-DA and SPLS-DA, in order to verify the properties of terpenes that explain their incorporation into micelles.Other multivariate statistical analysis, such as cluster analysis and PCA were used to study the structural variability of the selected compounds, as well as to determine if the calculated theoretical descriptors can describe all the structural characteristics of the terpenes. The study of thermodynamics of transfer of neutral solutes from the aqueous phase to the micellar phase has shown that even small structural differences of the molecules contain information about the distribution of the compounds in the micellar compartments. It was also possible to infer about the effect of ethanol on the partitions and on the micellar structure. The results for limonene showed the complexity involved in the partitions, showing that occurs volume restriction in alcohol-modified micelles. Results from LSER showed that the transfer of these compounds is mainly governed by hydrophobic interactions where Vx (McGowan volume) was selected as one of the most important descriptors to explain partition. The comparative analysis of the results obtained by the two methods (thermodynamic parameters studies and LSER) indicated similarity of results. This demonstrates the great reliability of the methods, and that similar studies using other micellar solutions and other classes of compounds (hormones, flavonoids, amines, etc.) might be very promising.

Atualmente cerca de 38,6 milhões de pessoas estão infectadas pelo vírus da síndrome da imunodeficiência adquirida (AIDS) em todo mundo. O único modo de tratamento para esta doença é através da utilização de medicamentos responsáveis por atuarem em diferentes pontos do ciclo replicativo do vírus. No Brasil esta doença é tratada como de calamidade pública, sendo seu tratamento feito através do programa nacional DST/AIDS, o qual distribui gratuitamente os medicamentos necessários para o tratamento. Tendo em vista que vários desses medicamentos são formulados pela indústria local, esta dissertação tem como objetivo o desenvolvimento de métodos analíticos passiveis de aplicação na rotina farmacêutica para a qualificação de matérias primas, bem como o controle de qualidade dos produtos acabados. As determinações nas formulações de nevirapina e lamivudina foram realizadas por CZE, em eletrólitos ácidos com pH < 2,5. Para a lamivudina a determinação foi realizada em um eletrólito de 0,5 % de TEA, 20 mmol.L-1 de TRIS, pH = 2,5, ajustado com ácido fosfórico, com um tempo de análise inferior a 4 minutos. O método desenvolvido para a nevirapina foi conduzido em um eletrólito de 10 mmol.L-1 de fosfato de sódio (pH =2,5), com um tempo de análise de 3 minutos. Um outro método foi desenvolvido permitindo a determinação de efavirenz, estavudina e ritonavir por MEKC, utilizando-se um planejamento fatorial 23 com ponto central, um tempo inferior a 9 minutos em um eletrólito consituído de 20 mmol.L-1 de tetraborato de sódio, 20 mmol.L-1 de SDS e 30 % de acetonitrila. Os métodos desenvolvidos foram validados de acordo com os protocolos oficiais, mostrando que estes métodos apresentam características adequadas para a análise de formulações farmacêuticas. Outra abordagem foi feita utilizando o acoplamento da eletroforese capilar à espectrometria de massas, onde amostras de urina fortificadas foram analisadas. As análise foram conduzidas utilizando 400 mmol.L-1 de ácido fórmico e líquido auxiliar constituído de 0,5 % de ácido fórmico diluído com uma solução metanol:água (1:1), permitindo a identificação inequívoca dos fármacos. / There are approximately 38.6 million people infected by the immunodeficiency acquired virus (AIDS) over the world. The only way of treatment for this illness is administrating drugs that act in different points of the replicative cycle of the virus. In Brazil this illness is dealt as public calamity, being its treatment made through the national program DST/AIDS, which distributes free of charge necessary medicines for the treatment. Considering that many of these drugs are formulated by the local industries, this thesis has as objective the development of analytical methods to be applied in the pharmaceutical routine for the qualification of raw materials, as well as the quality control of the finished products. The analysis of drug formulations of nevirapine and lamivudine were carried by CZE, in acid electrolytes with pH < 2.5. For lamivudine the analysis was carried using an electrolyte composed of 0.5 % of TEA, 20 mmol.L-1 of TRIS, pH = 2.5, adjusted with phosphoric acid, with an analysis time less than 4 minutes. The method developed for the nevirapine, was lead in an electrolyte composed of 10 mmol.L-1 of phosphate buffer (pH = 2.5), with a time of analysis of 3 minutes. Another method was developed for efavirenz, estavudine and ritonavir by MEKC, using 23 a factorial design with central point, with an analysis time less then 9 minutes in an electrolyte of 20 mmol.L-1 of sodium tetraborate, 20 mmol.L-1 sodium dodecyl sulfate and 30 % acetonitrile. The developed methods were validated in accordance with official protocols, showing that these methods can be advantageously used in the analysis of pharmaceutical formulations. Another approach was to use the coupling of capillary electrophoresis with mass spectrometry, where fortified samples of urine had been analyzed. The analysis were performed using 400 mmol.L-1 formic acid and liquid sheath consisting of 0.5 % of formic acid diluted with a solution of (1:1) methanol:water, allowing the unequivocal identification detection of the drugs in the samples.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-09T19:23:03Z No. of bitstreams: 1 carinadealmeidabastos.pdf: 1640331 bytes, checksum: 96c6f61dba624b337759b27baecc7a34 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T14:34:40Z (GMT) No. of bitstreams: 1 carinadealmeidabastos.pdf: 1640331 bytes, checksum: 96c6f61dba624b337759b27baecc7a34 (MD5) / Made available in DSpace on 2017-05-17T14:34:40Z (GMT). No. of bitstreams: 1 carinadealmeidabastos.pdf: 1640331 bytes, checksum: 96c6f61dba624b337759b27baecc7a34 (MD5) Previous issue date: 2015-03-20 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Um método cromatográfico eletrocinético micelar para a determinação simultânea do mesilato de nelfinavir e das impurezas ácido 3-hidroxi-2-metilbenzóico e benzoato de (2R,3R)-4-((3S,4aS,8aS)-3-(terc-butilcarbamoil)octahidroisoquinolina-2(1H)-il)-3-hidroxi-1-(feniltio)butano-2-amônio, com tempo de análise de 25 minutos, foi proposto. O eletrólito composto por tampão tetraborato de sódio (pH 9,24; 25 mmol L−1), dodecil sulfato de sódio (9 mmol L−1) e metanol (10%, v/v) foi otimizado utilizando planejamento fatorial misto, com detecção direta em 200 nm. Após avaliação das figuras de mérito seletividade, linearidade, precisão, limite de detecção, limite de quantificação, exatidão e robustez (Teste de Youden), o método foi aplicado na análise do mesilato de nelfinavir e suas impurezas em uma formulação farmacêutica (comprimidos). O método otimizado pode ser útil na determinação desses analitos em processos de monitoramento de síntese, matérias-primas e formulações farmacêuticas, oferecendo como vantagens baixo consumo de solventes, pequena demanda de amostra e uso de colunas não específicas. / A methodology for the simultaneous determination of nelfinavir mesylate and the impurities 3-hydroxy-2-methylbenzoic acid and (2R,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl) octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-(phenylthio)butan-2-aminium benzoate by micellar electrokinetic chromatography, with an analysis time of 25 min, was proposed. An electrolyte composed of sodium tetraborate buffer (pH 9.24; 25 mmol L−1), sodium dodecyl sulphate (9 mmol L−1) and methanol (10%, v/v) was optimized using a mixed-level factorial design, with direct detection at 200 nm. After evaluating some figures of merit, such as selectivity, linearity, precision, limit of detection, limit of quantification, accuracy and robustness (Youden’s test), the method was successfully applied to the analysis of nelfinavir mesylate and its impurities in a pharmaceutical formulation (tablets). The optimized methodology is demonstrated to be useful in the determination of these analytes in a synthesis monitoring process, in raw materials and in pharmaceutical formulations, while offering low solvent consumption, requiring a small sample and using non-specific columns as advantages.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Rupatadine is a second generation antihistamine H1, from the pyperidinic group, which inhibits both the histamine and platelet activating factor effects, and is clinically used for the treatment of allergic rhinitis and chronic urticaria. The methods for the evaluation of rupatadine in pharmaceutical products were developed and validated in the present work. The reversed-phase liquid chromatography (RP-LC) analysis was carried out using a Gemini C18 column (150 mm x 4.6 mm), maintained at 30 oC. The mobile phase consisted of ammonium acetate buffer 0.01 M, pH 3.0 with 0.05% of 1-heptanosulfonic acid/acetonitrile (71.5:28.5 v/v), run at a flow rate of 1.0 mL/min with detection at 242 nm. The chromatographic separation was obtained within 7 min and it was linear in the concentration range of 0.5-400 μg/mL (r2=0.9999). The capillary electrophoresis method was developed and validated, using the micellar electrokinetic chromatography (MEKC) as the separation mode, and nimesulide as internal standard (IS). The analysis were performed on a fused-silica capillary (50 μm id, effective length, 40 cm), maintained at 35ºC, using electrolyte solution consisted of 15 mM borate buffer and 25 mM anionic detergent SDS solution at pH 10, with detection by photodiode array detector set at 205 nm. The injection was performed using the hydrodynamic mode at 50 mbar for 5 s, and a constant voltage of 25 kV was applied during the analysis. The electrophoretic separation was obtained within 6 min and it was linear in the oncentration range of 0.5-150 μg/mL (r2=0.9996). The procedures were validated evaluating parameters such as the specificity, linearity, precision, accuracy, limits of detection and quantitation, robustness, and system suitability test, giving results within the acceptable range. The proposed methods were applied for the analysis of pharmaceutical products, showing significant correlation (P>0.05) of the results. Therefore, the procedures can be applied to improve the quality control of pharmaceutical products and to assure the safety and therapeutic efficacy of the drug. / A rupatadina é um anti-histamínico H1 de segunda geração pertencente ao grupo piperidínico, que inibe os efeitos da histamina e do fator ativador plaquetário, sendo utilizada clinicamente no tratamento de rinite alérgica e urticária crônica. No presente trabalho foram desenvolvidos e validados métodos para avaliação de rupatadina em produtos farmacêuticos. As análises por cromatografia líquida em fase reversa (CL-FR) foram realizadas utilizando coluna Gemini C18 (150 mm x 4,6 mm), mantida a 30 oC. A fase móvel foi composta de tampão acetato de amônio 0,01 M, pH 3,0 com 0,05% de ácido 1-heptanosulfônico/acetonitrila (71,5:28,5, v/v), eluída na vazão de 1,0 mL/min com detecção no ultravioleta a 242 nm. A separação cromatográfica foi obtida no tempo de 7 min, sendo linear na faixa de concentração de 0,5-400 μg/mL (r2=0,9999). Paralelamente, desenvolveu-se e validou-se método por eletroforese capilar, utilizando modo de separação por cromatografia eletrocinética micelar (MEKC) e nimesulida como padrão interno (PI). Executaram-se as análises em capilar de sílica fundida (50 μm id, comprimento efetivo de 40 cm), mantido a 35ºC, utilizando solução eletrolítica composta de tampão borato 15 mM e tensoativo aniônico SDS 25 mM, pH 10, com detecção no ultravioleta a 205 nm. A injeção foi realizada no modo hidrodinâmico a 50 mbar durante 5 s e voltagem constante de 25 kV foi aplicada durante as análises. A separação eletroforética foi obtida em 6 min, sendo linear na faixa de concentração de 0,5-150 μg/mL (r2=0,9996). Os procedimentos foram validados, avaliando-se os parâmetros de especificidade, linearidade, precisão, exatidão, limite de detecção e quantificação, robustez e teste de adequabilidade do sistema, cujos resultados cumpriram os requisitos preconizados. Os métodos propostos foram aplicados na análise de produtos farmacêuticos, demonstrando correlação significativa dos resultados (P>0,05). Desse modo, estabeleceram-se procedimentos que podem ser aplicados para aprimorar o controle da qualidade de medicamentos, bem como garantir a segurança e eficácia no uso terapêutico.

Capillary electrophoresis often uses complexing agents since the interaction between the analyte and the complexing agent can result in achieving or improving the separation. Examples of such methods can be electrokinetic chromatography or affinity capillary electrophoresis (ACE). ACE is used to determine the complexing parameters. In case of chiral separation, this issue gets complicated, since the parameters of the two analytes (enantiomers) are not completely independent to one another. Therefore, a procedure has been proposed in this thesis, that should always be used to evaluate the complexing parameters of two enantiomers. Statistical evaluation of these parameters was assessed as well. This work also proposes a method that allows to determine the relative migration order of two enantiomers in two different complexing separation systems. The mathematical description of electrophoresis is based on continuity equations, that are inherently nonlinear. However, these equations can be linearized to obtain an approximate analytical solution. There was recently presented a generalized model, that enables inclusion of complete complexing equilibria in the theoretical description of electromigration. Thus, various phenomena, including nonlinear ones, associated with complexation can be predicted. This...

No description available.