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Jesper Ostergaard

Publications and source records attributed to Jesper Ostergaard.

4 recordsLinked to original sources

CE frontal analysis based on simultaneous UV and contactless conductivity detection: a general setup for studying noncovalent interactions.

CE frontal analysis (CE-FA) has been established as a powerful tool to study noncovalent interactions between macromolecules and small molecules such as drug substances or pharmaceutical excipients. However, when using traditional commercial CE instrumentation, a serious drawback is related to the fact that only UV-active compounds can be studied. In recent years, contactless conductivity detection has become an attractive alternative to UV detection in CE due to its high versatility. In this study, we combine contactless conductivity detection and UV detection in a highly versatile setup for profiling noncovalent interactions between low-molecular-weight molecules and macromolecules. In the case of molecules having a chromophore the setup allows determination of binding constants using two independent detectors. The new contactless conductivity detection cell is compatible with commercial CE instrumentation and is therefore easily implemented in any analysis laboratory with CE expertise.

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Bioanalytical interaction studies executed by preincubation affinity capillary electrophoresis.

The versatility of CE is beneficial for the study of many types of molecular interactions, because different experimental designs can be made to suit the characteristics of a particular interaction. A very versatile starting point is the preequilibration type of affinity CE that has been used extensively for characterizing biomolecular interactions in the last 15 years. We review this field here and include a comprehensive overview of the existing preincubation ACE modes including their advantages and limitations as well as the methodological developments and applications within the bioanalytical field.

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Characterization of the rotating dialysis cell as an in vitro model potentially useful for simulation of the pharmacokinetic fate of intra-articularly administered drugs.

The rotating dialysis cell consisting of a donor and an acceptor compartment with volumes of 10 and 1000 ml, respectively, separated by a dialysis membrane is proposed as an in vitro model potentially useful for simulation of the events influencing drug residence time in the knee joint cavity after intra-articular instillation. The purpose of this study was to characterize the rotating dialysis cell model with respect to basic model and drug related factors affecting the rate of drug appearance in the acceptor phase after initial instillation of the solutes into the donor cell. A total of 15 model compounds were included in the study and it was revealed that the transport processes were governed by (i) the volume of the donor solution and (ii) the molecular weight of the diffusants. A relationship between the donor volume-independent permeability coefficient and the molecular weight of the diffusants has been established. Additionally, the model was robust with release kinetics being insensitive to changes in pH, ionic strength, viscosity of the release medium, and revolution speed of the donor cell. The characteristics of the rotating dialysis cell model suggest that it may be a useful tool in the design of innovative depot injectables in the area of local joint delivery.

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Effect of dextran as a run buffer additive in drug-protein binding studies using capillary electrophoresis frontal analysis.

The study of drug-protein interactions by capillary electrophoresis frontal analysis requires establishment of a sufficient mobility difference between the mobility of the ligand and protein. The potential utility of dextran as a run buffer additive to manipulate the electrophoretic mobilities of low molecular weight ligands and protein in capillary electrophoresis frontal analysis binding studies was assessed. It was demonstrated that dextran was effective in improving the separation between the ligands warfarin and flurbiprofen and human serum albumin. Separation of ligand and protein increased with the concentration of added dextran (0-7.5% (w/w)), while molecular weight of the additive (70,000-2,000,000) only had a minor effect. The effect of dextran addition on viscosity and electrophoretic and electroosmotic mobilites was systematically studied. Optimal frontal analysis settings were a compromise between achieving satisfactory separation and acceptable analysis times without loss of plateau peak conditions. No effect of dextran upon the drug-human serum albumin interactions could be detected for the model ligands. Introduction of dextran into the electrophoresis buffer expands the applicability of capillary electrophoresis frontal analysis in drug research to binding interactions between proteins and low molecular weight ligands possessing similar electrophoretic mobilities.

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