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Method for Immobilization of Liposomes in Capillary Electrophoresis by Electrostatic Interaction with Derivatized Agarose
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
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2002 In: Electrophoresis, Vol. 23, no 19, p. 3381-3384Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 23, no 19, p. 3381-3384
Identifiers
URN: urn:nbn:se:uu:diva-91395OAI: oai:DiVA.org:uu-91395DiVA, id: diva2:164110
Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved
In thesis
1. Physicochemical and Biopharmaceutical Characterisation of Small Drug Molecules by Capillary Electrophoresis
Open this publication in new window or tab >>Physicochemical and Biopharmaceutical Characterisation of Small Drug Molecules by Capillary Electrophoresis
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. p. 56
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 947
Keywords
Analytical chemistry, capillary electrophoresis (CE), micellar electrokinetic chromatography (MEKC), drug, liposome, microemulsion, coating, pKa, lipophilicity, multivariate analysis, molecular descriptor, hierarchical analysis, passiv absorption, Analytisk kemi
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-4008 (URN)91-554-5881-5 (ISBN)
Public defence
2004-03-05, B:22, BMC, Husargatan 3, Uppsala, 10:15
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Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved

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