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Sensitivity enhancement of capillary electrophoresis‐frontal analysis based method for characterization of drug‐protein interactions using on‐line sample preconcentration

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Authors

BRŽEZICKÁ Taťána GLATZ Zdeněk KOHÚTOVÁ Lenka

Year of publication 2023
Type Article in Periodical
Magazine / Source JOURNAL OF SEPARATION SCIENCE
MU Faculty or unit

Faculty of Science

Citation
Web https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/jssc.202300152?campaign=woletoc
Doi http://dx.doi.org/10.1002/jssc.202300152
Keywords binding constants; capillary electrophoresis-frontal analysis; human serum albumin; on-line preconcentration
Description Capillary electrophoresis-frontal analysis is one of the most frequently used approach for the study of plasma protein-drug interactions as a substantial part of the new drug development. However, the capillary electrophoresis-frontal analysis typically combined with ultraviolet visible detection suffers from insufficient concentration sensitivity particularly for substances with limited solubility and low molar absorption coefficient. The sensitivity problem has been solved in this work by its combination with an on-line sample preconcentration. According the knowledge of the authors this combination has never been used to characterize plasma protein-drug binding. It resulted into a fully automated and versatile methodology for the characterization of binding interactions. Further, the validated method minimalizes the experimental errors due to a reduction in the manipulation of samples. Moreover, employing an on-line preconcentration strategy with capillary electrophoresis-frontal analysis using human serum albumin-salicylic acid as a model system improves the drug concentration sensitivity 17 fold compared to the conventional method. The value of binding constant (1.51 ± 0.63)?104 L/mol obtained by this new capillary electrophoresis-frontal analysis modification is in agreement with the value (1.13 ± 0.28)?104 L/mol estimated by conventional variant of capillary electrophoresis-frontal analysis without the preconcentration step, as well as with literature data obtained using different techniques.
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