La nécessité de garantir la qualité des médicaments antipaludiques disponibles sur le marché pharmaceutique d'Afrique subsaharienne est l'une des stratégies mises en œuvre pour réduire les taux élevés de morbidité et de mortalité liés au paludisme. L'objectif de ce travail de thèse était de proposer des méthodes de dosage par électrophorèse capillaire (EC) de combinaisons antipaludiques à base de sulfadoxine/pyriméthamine (SDX/PYR), artésunate/amodiaquine (AS/AQ) et artéméther/luméfantrine (AM/LUM) retenues dans le schéma thérapeutique ivoirien et commercialisées sous forme de comprimés.Cet objectif a été atteint en employant trois modes de séparation : l'électrophorèse capillaire de zone (CZE) pour SDX/PYR, la chromatographie électrocinétique micellaire (MEKC) pour AS/AQ et la chromatographie électrocinétique par microémulsion (MEEKC) pour AM/LUM. Les méthodes développées ont été validées selon les règles d'ICH et appliquées à des comprimés provenant d'officines ou vendues sur les marchés de rue en Côte d'Ivoire. Elles présentent une répétabilité satisfaisante (CV < 3%, n = 7 procédures analytiques). La méthode de CZE qui utilise un tampon pH 7 pour la séparation de SDX et PYR a donné des résultats de dosage concordants avec la méthode de chromatographie liquide décrite dans l'USP-NF. Sur les neuf formulations de comprimés analysées, une formulation prélevée dans le marché de rue s'est révélée sous-dosée en SDX. La méthode MEKC utilisant le dodécylsulfate de sodium (SDS) dans un tampon borate pH 9,2 a permis le dosage d'AS et AQ. L'application à l'analyse de quatre formulations issues de l'officine a donné des teneurs en AS et AQ conformes aux teneurs déclarées. Enfin, la microémulsion octane-butanol-SDS-tampon borate en MEEKC s'est révélée appropriée au dosage d'AM et LUM, molécule très hydrophobe. L'application à l'analyse de quatre formulations prélevées à l'officine a révélé des teneurs conformes aux teneurs déclarées et la présence dans une formulation d'un ingrédient non déclaré. Le potentiel de screening de cette méthode MEEKC, évalué sur 22 antipaludiques et la sulfaméthoxazole et la triméthoprime, a donné une résolution partielle ou totale pour 17 composés.L'EC peut être utilisée comme technique alternative à la chromatographie liquide pour le contrôle des antipaludiques retenus dans le schéma thérapeutique ivoirien. / The need to ensure the quality of antimalarials available on the pharmaceutical market in sub-Saharan Africa is one of the strategies implemented to reduce the high morbidity and mortality rates associated with malaria. The aim of this thesis was to propose capillary electrophoresis (CE) methods for the determination of combinations of antimalarials containing sulfadoxine/pyrimethamine (SDX/PYR), artesunate/amodiaquine (AS/AQ) and artemether/lumefantrine (AM/LUM) recommended in the Côte d'Ivoire therapeutic protocol and marketed as tablets.The objective was achieved by employing three separation modes: capillary zone electrophoresis (CZE) for SDX/PYR, micellar electrokinetic chromatography (MEKC) for AS/AQ and microemulsion electrokinetic chromatography (MEEKC) for AM/LUM. The developed methods were validated according to ICH rules and were applied to various tablet formulations bought in pharmacies or on the street-market in Côte d'Ivoire. The methods presented satisfactory repeatability values (CV <3%, n = 7 analytical procedures). CZE method used a buffer of pH 7 for the simultaneous separation of SDX and PYR and gave results that were compliant with the dosage by the liquid chromatography method described in the U.S. Pharmacopoeia. Of the nine tablet formulations analyzed, one formulation bought on the street-market had a low SDX content. An MEKC method using SDS in a borate buffer pH 9.2 allowed the determination of AS and AQ in bilayer tablets. Application to four commercial formulations with different dosages gave a content in good agreement with the declared content. Finally, butanol-octane-SDS-borate buffer microemulsion in MEEKC was found to be suitable for the determination of AM and LUM, a very hydrophobic compound. Application to four commercial tablet formulations gave a content in good agreement with the declared content and evidenced the presence in a formulation of an undeclared ingredient. The potential screening capacity of this MEEKC method was evaluated on 22 antimalarials and on sulfamethoxazole and trimethoprim. Partial or complete resolution of 17 compounds was obtained.CE can be used as an alternative technique to liquid chromatography for the control of antimalarial drugs recommended in the national therapeutic protocol against malaria.

No primeiro capitulo deste trabalho, é apresentada a classificação e a importância dos esteróides sexuais para manutenção da vida humana. Na seqüência, o próximo capítulo mostra aspectos gerais sobre eletroforese capilar, tais como modo de operação, terminologia utilizada e considerações sobre o fluxo eletrosmótico e mobilidade eletroforética. O terceiro capítulo exibe um estudo da interação solvente/micela de SDS/soluto, baseado na otimização da geometria da molécula, análise conformacional, com descritores moleculares e modelos de regressão, baseados no coeficiente de partição. Foram realizadas medidas experimentais dos tempos de retenção, de onze esteróides, a partir da MEKC, em eletrólitos modificados por solvente, conforme suas propriedades de seletividade. O efeito do solvente na modulação da retenção do soluto foi discutido em termos da LSER, a qual indicou a concentração total de solvente no meio como o principal fator de controle do tempo de retenção. A separação dos compostos selecionados, na melhor condição, foi testada em um extrato de uma amostra de urina obtida de um voluntário humano - sexo feminino - em fase de puberdade. A composição do eletrólito (20 mmol L-1 SDS, 20% EtOH e 20 mmol L-1 tetraborato de sódio a pH 9,4) proposta pode ser aplicada potencialmente para a determinação de estrógenos em estudos clínicos (0.80% C.V. para tempo de migração e 2.5% C.V. para área do pico, n = 5). Posteriormente, já no quarto capítulo, o uso do planejamento fatorial foi uma forma rápida de otimizar a composição do eletrólito para separar uma mistura-teste com onze esteróides. Uma triagem das variáveis indicou que as concentrações de ACN, SDS e &#946;-CD mais influenciavam a resolução e o tempo de análise. O estudo dos efeitos mostrou que a interação ACN/ &#946;-CD e a ACN mais contribuía para resolução dos pares críticos. O sistema micelar constituído por 20 mmol L-1 SDS, 10% ACN, 5 mmolL-1 &#946;-CD e 20 mmolL-1 TBS, pH 9.2, foi o meio no qual se obteve a melhor resposta em relação à resolução dos pares críticos e tempo de análise Este método foi usado avaliar a presença dos esteróides em extrato etanólico de excrementos de Pantera onca. Em outra etapa um método MEEKC foi desenvolvido e validado para a determinação de 17 &#946;-estradiol em adesivo transdérmico usando uma microemulsão contendo 0.5% (m/m) acetato de etila, 1.2% (m/m) butan-1-ol, 0.6% (m/m) SDS, 15% (v/v) ACN e 82.7% (m/m) TBS 12 mmol L-1 , pH 9.4. Foi obtida aceitável precisão (<1.2% RSD), linearidade, sensibilidade (LOD=0.89 &#181;g/mL; LOQ=2.68 &#181;g/mL) e recuperação (100.4 &#177;0.9 %). Por fim, o ultimo capítulo traz o desenvolvimento e validação de um método via MEKC para determinação etinilestradiol em comprimidos usando um eletrólito constituído por 20 mmol L-1 SDS, 22,5 % (v/v) ACN e 10 mmol L-1 TBS, pH 9,2. Apresentando valores de precisão (<1.0% RSD), linearidade, sensibilidade (LOD=0.84 &#181;g/mL; LOQ=2.55 &#181;g/mL) e recuperação (99.4&#177; 0.7 %) aceitáveis. E ainda, via MEEKC, para determinação simultânea de etinilestradiol e levonorgestrel usando uma microemulsão contendo: 0.5% (m/m) acetato de etila, 1.2% (m/m) butan-1-ol, 0.6% (m/m) de SDS, 15% (v/v) etanol e 82.7% (m/m) TBS 12 mmol L-1 , pH 9.2. Injeção: pelo outlet 3s/0.5 psi. Com alta precisão (<0.8% RSD), linearidade, sensibilidade (LOD=1.04 &#181;g/mL; LOQ=3.15 &#181;g/mL para etinilestradiol e LOD=1.35 &#181;g/mL; LOQ=4.10 &#181;g/mL para o levonorgestrel) e recuperação (98.6&#177; 0.8 % para etinilestradiol), os métodos mostraram-se sensíveis e precisos para serem utilizados no controle de qualidade de formulações farmacêuticas. / In the first chapter of this work, the classification and importance of the sexual steroids for maintenance of the life human is presented. The next chapter presents general aspects on capillary electrophoresis, such as operation, terminology and considerations on the electroosmotic flow and electroforetic mobility. The third chapter shows a study of interaction solvent/ SDS micelle /solute, based on the optimization of molecule geometry, conformational analysis, with molecular descriptors and regression models, based in the partition coefficient. The retention times were measured experimentally for eleven steroids, in MEKC electrolytes modified by solvents. The solvent effect in modulating the retention of solute was explaned in terms of LSER, which indicated the total organic solvent percentage in the electrolyte as the main factor controlling retention. The separation of selected compounds, in the best condition, was tested in urine extract sample from a human volunteer - feminine -1 sex - in puberty phase. The composition of the proposed electrolyte (20 mmol L-1 SDS, 20% (v/v) EtOH and 20 mmol L-1 sodium tetraborate, pH 9.4) can potentially be applied for determination of estrogens in clinical studies (0.80% C.V. for migration time and 2.5% C.V. for peak area, n = five consecutive injections). Later, in fourth chapter, the use of factorial design was introduced to optimize the composition of the electrolyte to separate a mixture-test with eleven steroids. The selection of variable indicated that the concentrations of ACN, SDS and &#946;-CD influenced the most resolution and analysis time. The study of the effect showed that interaction ACN/ &#946;-CD and ACN were important for resolution of the critical pairs. The micelle system constituted of 20 mmol L-1 SDS, 10% (v/v) ACN, 5 mmolL-1 &#946;-CD and 20 mmolL-1 TBS, pH 9.2, was composition to achieve resolution of the critical pairs and analysis time. This method was used to evaluate the presence of the steroids in fecal ethanolic extract of Pantera onca. In another work a MEEKC method was developed and validated for determination of 17 &#946;-estradiol in transdermical adhesive using a microemulsion containing 0.5% (w/w) ethyl acetate, 1.2% (w/w) butan-1-ol, 0.6% (w/w) sodium dodecyl sulfate, 15% (v/v) ACN and 82.7% (w/w) 12 mmol L-1 sodium tetraborate aqueous buffer at pH 9.4. Acceptable precision (<1.2% RSD), linearity, sensitivity (LOD=0.89 &#181;g/mL; LOQ=2.68 &#181;g/mL) and recovery (100.4&#177; 0.9 % at three concentration levels) were obtained. The last chaper, the development and validation of MEKC method for determination of ethynylestradiol in a commercial tablet formulation using a micellar medium containing, 25 mmol L-1 sodium dodecyl sulfate, 22,5% (v/v) ACN and 10 mmol L-1 sodium tetraborate aqueous buffer at pH 9.2 was presented. Acceptable precision (<1.0% RSD), linearity, sensitivity (LOD=0.84 &#181;g/mL; LOQ=2.55 &#181;g/mL) and recovery (99.8&#177; 1.8 % at three concentration levels) were obtained. A MEEKC method for the simultaneous determination of ethynylestradiol and levonorgestrel using microemulsion containing 0.5% (w/w) ethyl acetate, 1.2% (w/w) butan-1-ol, 0.6% (w/w) sodium dodecyl sulfate, 15% (v/v) ethanol and 82.7% (w/w) 12 mmol L-1 sodium III tetraborate aqueous buffer at pH 9.2 was developed. High precision (<0.8% RSD), linearity, sensitivity (LOD=1.04 &#181;g/mL; LOQ=3.15 &#181;g/mL to ethynylestradiol and LOD=1.35 &#181;g/mL; LOQ=4.10 &#181;g/mL to levonorgestrel) and recovery (98.6&#177; 0.8 % at three concentration levels of ethynylestradiol) were obtained.

No primeiro capitulo deste trabalho, é apresentada a classificação e a importância dos esteróides sexuais para manutenção da vida humana. Na seqüência, o próximo capítulo mostra aspectos gerais sobre eletroforese capilar, tais como modo de operação, terminologia utilizada e considerações sobre o fluxo eletrosmótico e mobilidade eletroforética. O terceiro capítulo exibe um estudo da interação solvente/micela de SDS/soluto, baseado na otimização da geometria da molécula, análise conformacional, com descritores moleculares e modelos de regressão, baseados no coeficiente de partição. Foram realizadas medidas experimentais dos tempos de retenção, de onze esteróides, a partir da MEKC, em eletrólitos modificados por solvente, conforme suas propriedades de seletividade. O efeito do solvente na modulação da retenção do soluto foi discutido em termos da LSER, a qual indicou a concentração total de solvente no meio como o principal fator de controle do tempo de retenção. A separação dos compostos selecionados, na melhor condição, foi testada em um extrato de uma amostra de urina obtida de um voluntário humano - sexo feminino - em fase de puberdade. A composição do eletrólito (20 mmol L-1 SDS, 20% EtOH e 20 mmol L-1 tetraborato de sódio a pH 9,4) proposta pode ser aplicada potencialmente para a determinação de estrógenos em estudos clínicos (0.80% C.V. para tempo de migração e 2.5% C.V. para área do pico, n = 5). Posteriormente, já no quarto capítulo, o uso do planejamento fatorial foi uma forma rápida de otimizar a composição do eletrólito para separar uma mistura-teste com onze esteróides. Uma triagem das variáveis indicou que as concentrações de ACN, SDS e &#946;-CD mais influenciavam a resolução e o tempo de análise. O estudo dos efeitos mostrou que a interação ACN/ &#946;-CD e a ACN mais contribuía para resolução dos pares críticos. O sistema micelar constituído por 20 mmol L-1 SDS, 10% ACN, 5 mmolL-1 &#946;-CD e 20 mmolL-1 TBS, pH 9.2, foi o meio no qual se obteve a melhor resposta em relação à resolução dos pares críticos e tempo de análise Este método foi usado avaliar a presença dos esteróides em extrato etanólico de excrementos de Pantera onca. Em outra etapa um método MEEKC foi desenvolvido e validado para a determinação de 17 &#946;-estradiol em adesivo transdérmico usando uma microemulsão contendo 0.5% (m/m) acetato de etila, 1.2% (m/m) butan-1-ol, 0.6% (m/m) SDS, 15% (v/v) ACN e 82.7% (m/m) TBS 12 mmol L-1 , pH 9.4. Foi obtida aceitável precisão (<1.2% RSD), linearidade, sensibilidade (LOD=0.89 &#181;g/mL; LOQ=2.68 &#181;g/mL) e recuperação (100.4 &#177;0.9 %). Por fim, o ultimo capítulo traz o desenvolvimento e validação de um método via MEKC para determinação etinilestradiol em comprimidos usando um eletrólito constituído por 20 mmol L-1 SDS, 22,5 % (v/v) ACN e 10 mmol L-1 TBS, pH 9,2. Apresentando valores de precisão (<1.0% RSD), linearidade, sensibilidade (LOD=0.84 &#181;g/mL; LOQ=2.55 &#181;g/mL) e recuperação (99.4&#177; 0.7 %) aceitáveis. E ainda, via MEEKC, para determinação simultânea de etinilestradiol e levonorgestrel usando uma microemulsão contendo: 0.5% (m/m) acetato de etila, 1.2% (m/m) butan-1-ol, 0.6% (m/m) de SDS, 15% (v/v) etanol e 82.7% (m/m) TBS 12 mmol L-1 , pH 9.2. Injeção: pelo outlet 3s/0.5 psi. Com alta precisão (<0.8% RSD), linearidade, sensibilidade (LOD=1.04 &#181;g/mL; LOQ=3.15 &#181;g/mL para etinilestradiol e LOD=1.35 &#181;g/mL; LOQ=4.10 &#181;g/mL para o levonorgestrel) e recuperação (98.6&#177; 0.8 % para etinilestradiol), os métodos mostraram-se sensíveis e precisos para serem utilizados no controle de qualidade de formulações farmacêuticas. / In the first chapter of this work, the classification and importance of the sexual steroids for maintenance of the life human is presented. The next chapter presents general aspects on capillary electrophoresis, such as operation, terminology and considerations on the electroosmotic flow and electroforetic mobility. The third chapter shows a study of interaction solvent/ SDS micelle /solute, based on the optimization of molecule geometry, conformational analysis, with molecular descriptors and regression models, based in the partition coefficient. The retention times were measured experimentally for eleven steroids, in MEKC electrolytes modified by solvents. The solvent effect in modulating the retention of solute was explaned in terms of LSER, which indicated the total organic solvent percentage in the electrolyte as the main factor controlling retention. The separation of selected compounds, in the best condition, was tested in urine extract sample from a human volunteer - feminine -1 sex - in puberty phase. The composition of the proposed electrolyte (20 mmol L-1 SDS, 20% (v/v) EtOH and 20 mmol L-1 sodium tetraborate, pH 9.4) can potentially be applied for determination of estrogens in clinical studies (0.80% C.V. for migration time and 2.5% C.V. for peak area, n = five consecutive injections). Later, in fourth chapter, the use of factorial design was introduced to optimize the composition of the electrolyte to separate a mixture-test with eleven steroids. The selection of variable indicated that the concentrations of ACN, SDS and &#946;-CD influenced the most resolution and analysis time. The study of the effect showed that interaction ACN/ &#946;-CD and ACN were important for resolution of the critical pairs. The micelle system constituted of 20 mmol L-1 SDS, 10% (v/v) ACN, 5 mmolL-1 &#946;-CD and 20 mmolL-1 TBS, pH 9.2, was composition to achieve resolution of the critical pairs and analysis time. This method was used to evaluate the presence of the steroids in fecal ethanolic extract of Pantera onca. In another work a MEEKC method was developed and validated for determination of 17 &#946;-estradiol in transdermical adhesive using a microemulsion containing 0.5% (w/w) ethyl acetate, 1.2% (w/w) butan-1-ol, 0.6% (w/w) sodium dodecyl sulfate, 15% (v/v) ACN and 82.7% (w/w) 12 mmol L-1 sodium tetraborate aqueous buffer at pH 9.4. Acceptable precision (<1.2% RSD), linearity, sensitivity (LOD=0.89 &#181;g/mL; LOQ=2.68 &#181;g/mL) and recovery (100.4&#177; 0.9 % at three concentration levels) were obtained. The last chaper, the development and validation of MEKC method for determination of ethynylestradiol in a commercial tablet formulation using a micellar medium containing, 25 mmol L-1 sodium dodecyl sulfate, 22,5% (v/v) ACN and 10 mmol L-1 sodium tetraborate aqueous buffer at pH 9.2 was presented. Acceptable precision (<1.0% RSD), linearity, sensitivity (LOD=0.84 &#181;g/mL; LOQ=2.55 &#181;g/mL) and recovery (99.8&#177; 1.8 % at three concentration levels) were obtained. A MEEKC method for the simultaneous determination of ethynylestradiol and levonorgestrel using microemulsion containing 0.5% (w/w) ethyl acetate, 1.2% (w/w) butan-1-ol, 0.6% (w/w) sodium dodecyl sulfate, 15% (v/v) ethanol and 82.7% (w/w) 12 mmol L-1 sodium III tetraborate aqueous buffer at pH 9.2 was developed. High precision (<0.8% RSD), linearity, sensitivity (LOD=1.04 &#181;g/mL; LOQ=3.15 &#181;g/mL to ethynylestradiol and LOD=1.35 &#181;g/mL; LOQ=4.10 &#181;g/mL to levonorgestrel) and recovery (98.6&#177; 0.8 % at three concentration levels of ethynylestradiol) were obtained.

Capillary electrophoresis (CE) is an analytical chemistry approach that allows for the efficient separation by charge of diverse classes of compounds for analysis, including secondary metabolites. The goal of this work was to optimize a buffer system for plant tissue analysis using micellar electrokinetic chromatography (MEKC), and by doing so to understand the role of buffer components in the performance of this form of capillary electrophoresis. In this experiment we implemented a factorial design to optimize buffer composition for separating plant tissue and secondary metabolites. The results of this experiment will be used to optimize a universal buffer for MEKC analysis that can be used on any variety of plant tissues. To determine the feasibility of this, a diverse set of plant secondary metabolite chemical standards in solution were tested as well as Helianthus annuus tissue to confirm the separation in a real biological sample. The results of this optimization yield insights into the utility of buffer components like electrolyte and pH for MEKC separation.

Micellar electrokinetic chromatography (MEKC), one of the major capillary electrophoresis (CE) modes, has been interfaced to mass spectrometry (MS) to provide high sensitivity and selectivity for analysis of chiral compounds. The research in this dissertation presents the development of novel polymeric glucopyranoside based molecular micelles (MoMs) (aka. polymeric surfactants) and their application in chiral MEKC-MS. Chapter 1 is a review of chiral CE-MS - in the period 2010-2015. In this chapter, the fundamental of chiral CE and CE-MS is illustrated and the recent developments of chiral selectors and their applications in chiral EKC-MS, CEC-MS and MEKC-MS are discussed in details. Chapter 2 introduces the development of a novel polymeric α-D-glucopyranoside based surfactants, n-alkyl-α-D-glucopyranoside 4,6-hydrogen phosphate, sodium salt. In this chapter, polymeric α-D-glucopyranoside-based surfactants with different chain length and head groups have been successfully synthesized, characterized and applied as compatible chiral selector in MEKC-ESI-MS/MS. or the enantioseparation of ephedrines and β-blockers. Chapter 3 continues to describe the employment of polymeric glucopyranoside based surfactants as chiral selector in MEKC-MS/MS. The polymeric β-D-glucopyranoside based surfactants, containing charged head groups such as n-alkyl β-D-glucopyranoside 4,6-hydrogen phosphate, sodium salt and n-alkyl β-D-glucopyranoside 6-hydrogen sulfate, monosodium salt were able to enantioseparate 21 cationic drugs and 8 binaphthyl atropisomers (BAIs) in MEKC-MS/MS, which promises to open up the possibility of turning an analytical technique into high throughput screening of chiral compounds. Physicochemical properties and enantioseparation capability of polymeric β-D-glucopyranoside based surfactants with different head groups and chain lengths were compared. Moreover, the comparison of polymeric α- and β-D-glucopyranoside 4,6-hydrogen phosphate, sodium salt were further explored with regard to enantioseparations of ephedrine alkaloids and b-blockers. The concept of multiplex chiral MEKC-MS for high throughput quantitation is demonstrated for the first time in scientific literature.

Orientadora: Elizabete Campos de Lima / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Ciência e Tecnologia/ Química

<p>Capillary Electrophoresis (CE) was explored as a means for physicochemical and biopharmaceutical characterisation of small drug molecules. Special attention was paid to the characterisation of acid-base and lipophilic properties of drug compounds by analysing their migration behaviour in different CE systems. The thesis comprises an overview of the field together with separate studies on the different topics.</p><p>The utility of CE for the determination of pK_a of labile drug compounds was investigated. A general methodology was developed comprising key steps such as the use of a stabilising sample diluent, electromigration injection, and analyte characterisation by UV-Vis spectroscopy. The methodology was successfully applied for two sets of drug compounds, labile at low and high pH, respectively.</p><p>CE was also evaluated for experimental modelling of passive intestinal membrane permeability by studying analyte migration in liposomal, microemulsion and micellar electrolytes. Good correlation is reported between CE migration and Caco-2 cell absorption estimates and for in vitro inhibition of thrombin. Interestingly, a slightly better correlation was obtained for liposomal electrolytes.</p><p>The utility of liposomes in CE was further extended by developing a novel procedure for immobilising liposomes inside fused silica capillaries. This approach enabled direct on-line coupling of liposome CE to high sensitivity mass spectrometry. The utility of liposome-coated capillaries is demonstrated for estimating drug passive intestinal membrane permeability. Its use in biopharmaceutical drug profiling is discussed.</p><p>Utilising advanced molecular descriptors, commonly applied to in silico prediction of passive intestinal membrane permeability, migration of analytes in micellar CE systems could be well predicted. The novel approach was based on hierarchical multivariate analytics and use of molecular descriptors for both analytes and micellar media surfactants. Demonstrated results propose that the CE format could be useful to validate how representative molecular descriptors are for describing molecular behaviour in complex liquid media, e.g. physiological systems.</p>

Capillary Electrophoresis (CE) was explored as a means for physicochemical and biopharmaceutical characterisation of small drug molecules. Special attention was paid to the characterisation of acid-base and lipophilic properties of drug compounds by analysing their migration behaviour in different CE systems. The thesis comprises an overview of the field together with separate studies on the different topics. The utility of CE for the determination of pKa of labile drug compounds was investigated. A general methodology was developed comprising key steps such as the use of a stabilising sample diluent, electromigration injection, and analyte characterisation by UV-Vis spectroscopy. The methodology was successfully applied for two sets of drug compounds, labile at low and high pH, respectively. CE was also evaluated for experimental modelling of passive intestinal membrane permeability by studying analyte migration in liposomal, microemulsion and micellar electrolytes. Good correlation is reported between CE migration and Caco-2 cell absorption estimates and for in vitro inhibition of thrombin. Interestingly, a slightly better correlation was obtained for liposomal electrolytes. The utility of liposomes in CE was further extended by developing a novel procedure for immobilising liposomes inside fused silica capillaries. This approach enabled direct on-line coupling of liposome CE to high sensitivity mass spectrometry. The utility of liposome-coated capillaries is demonstrated for estimating drug passive intestinal membrane permeability. Its use in biopharmaceutical drug profiling is discussed. Utilising advanced molecular descriptors, commonly applied to in silico prediction of passive intestinal membrane permeability, migration of analytes in micellar CE systems could be well predicted. The novel approach was based on hierarchical multivariate analytics and use of molecular descriptors for both analytes and micellar media surfactants. Demonstrated results propose that the CE format could be useful to validate how representative molecular descriptors are for describing molecular behaviour in complex liquid media, e.g. physiological systems.