| Abstract
| - The principles for evaluation of conditional associationconstants between drug enantiomers and proteins, exemplified here by α1-acid glycoprotein (AGP), usingcapillaryzone electrophoresis employing a partial fillingtechnique,is presented. In the partial filling technique only thefirstpart of the capillary is filled with the selector, andthisselector zone (plug) length can be varied by introducingthe selector solution at different times at constant pressure. An important feature of the technique is the lowconsumption of selector solution in this study only 40−290 nL is used per run, of special importance when theavailability of the selector is limited, and also in case itisexpensive. Conditions are chosen so that the proteinhasa net negative charge and migrates toward the anode,while the analytes migrate toward the detector at thecathodic side. The resolution is linearly related totheeffective plug length, as shown in separations of theenantiomers of disopyramide and remoxipride. The effective plug length can be calculated, which forms thebasis to apply this technique for determinations of association constants. The association between the enantiomers of the solutes and AGP varied with increasingtemperature, as shown by determined association constants. It was found that the association between theenantiomers and AGP was strongest at 25 °C and decreased at both lower and higher temperatures. Thisunexpected finding may indicate conformational changesof the protein with temperature variations.
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