Affinity capillary electrophoresis and fluorescence spectroscopy for studying enantioselective interactions between omeprazole enantiomer and human serum albumin

Abstract

Baseline separation of omeprazole (OME) enantiomers was achieved by affinity capillary electrophoresis (ACE), using human serum albumin (HSA) as the chiral selector. The influence of several experimental variables such as HSA concentration, the type and content of organic modifiers, applied voltage and running buffer concentration on the separation was evaluated. The binding of esomeprazole (S-omeprazole, S-OME) and its R-enantiomer (R-omeprazole, R-OME) to HSA under simulated physiological conditions was studied by ACE and fluorescence spectroscopy which was considered as a reference method. ACE studies demonstrated that the binding constants of the two enantiomers and HSA were 3.18 × 10 M and 5.36 × 10 M , respectively. The binding properties including the fluorescence quenching mechanisms, binding constants, binding sites and the number of binding sites were obtained by fluorescence spectroscopy. Though the ACE method could not get enough data when compared with the fluorescence spectrum method, the separation and binding studies of chiral drugs could be achieved simultaneously via this method. This study is of great significance for the investigation and clinical application of chiral drugs.

Investigation of the enantioselective interaction between selected drug enantiomers and human serum albumin by mobility shift‐affinity capillary electrophoresis

“…The extent of adsorption might increase in the presence of more amino groups and an overall more positive charge on proteins. In this study, sufficient rinsing between runs using SDS was applied to remove the adsorbed HSA and ensure the repeatability [26,30]. SDS has shown effectiveness in washing a capillary wall by the combination of denaturation proteins and micellar effect [26].…”

“…In this study, sufficient rinsing between runs using SDS was applied to remove the adsorbed HSA and ensure the repeatability [26,30]. SDS has shown effectiveness in washing a capillary wall by the combination of denaturation proteins and micellar effect [26]. Accordingly, HSA adsorption onto the capillary wall was minimized, which prevented the separation system from severe peak broadening.…”

“…Among the established methods of binding studies [24], ACE is well suited to enantiomeric separations [25] and simultaneous binding constant determination [26,27]. ACE offers various separation modes in the field of enantioselective investigation [24,27].…”

“…In terms of the protein additive in the BGE for a direct separation, ACE is also known as mobility shift-affinity CE (ms-ACE) [30,31]. A baseline enantiomeric separation of omeprazole using HSA as a CS was achieved by ms-ACE mode [26].…”

Predefine resolution of enantiomers in partial filling capillary electrophoresis and two discontinuous function plugs coupling in‐capillary

“…The enantioseparation of chiral compounds is very important in pharmaceutical industry . CE has proved to be one of the most effective methods for enantiomers' separation due to its high efficiency, robustness, low cost, simplicity, and diversity regarding different modes, such as ACE , MEKC , and NACE . The enantioseparation can be achieved using different types of chiral selectors, such as cyclodextrin and its derivatives , cyclofructans , crown ether , DNA , macrocyclic antibiotics , ionic liquids , chiral metal‐ion complexes , and proteins .…”