Evaluation of association constants between drug enantiomers and human alpha 1-acid glycoprotein by applying a partial-filling technique in affinity capillary electrophoresis

Analytical Chemistry
A Amini, D Westerlund

Abstract

The principles for evaluation of conditional association constants between drug enantiomers and proteins, exemplified here by alpha 1-acid glycoprotein (AGP), using capillary zone electrophoresis employing a partial filling technique, is presented. In the partial filling technique only the first part of the capillary is filled with the selector, and this selector zone (plug) length can be varied by introducing the selector solution at different times at constant pressure. An important feature of the technique is the low consumption of selector solution in this study only 40-290 nL is used per run, of special importance when the availability of the selector is limited, and also in case it is expensive. Conditions are chosen so that the protein has a net negative charge and migrates toward the anode, while the analytes migrate toward the detector at the cathodic side. The resolution is linearly related to the effective plug length, as shown in separations of the enantiomers of disopyramide and remoxipride. The effective plug length can be calculated, which forms the basis to apply this technique for determinations of association constants. The association between the enantiomers of the solutes and AGP varied with increasing tempe...Continue Reading

Citations

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