Study of protein–drug binding by capillary zone electrophoresis: Prospects and problems

Abstract

The free drug concentration is usually significantly smaller than the overall concentration because most drugs are, during their transport through the blood circulation, reversibly bound to blood constituents particularly the plasma proteins, albumin and a-acid glycoproteins. An alternative separation technique to study protein–drug interactions is capillary zone electrophoresis (CZE). It is a very simple and extremely efficient separation technique capable of separating a drug and its protein–drug complex according to their net charge and size difference. The CZE principle is based on the separation of the drug, the protein and the protein–drug complex on the basis of their difference in electrophoretic mobilities, which depend on the net charge and size of the compounds. The CZE methods described below can only be applied when the protein and protein–drug complex have very close electrophoretic mobilities, e.g. when the charge and size of the protein is not significantly changed by adsorbed drug molecules.