Enantiomeric Separation of Basic Drugs with Partially Filled Serum Albumin as Chiral Selector in Capillary Electrophoresis

Abstract

A reliable method is presented for the chiral separation of three basic drugs (mexiletine, chlorpheniramine and propranolol) with serum albumins (human and porcine, HSA and PSA) as chiral selectors by capillary electrophoresis in combination with the partial filling technique. Based on the systematic optimization of operation variables, the chiral separation of mexiletine, chlorpheniramine and propranolol was achieved in the pH 7.4 phosphate buffer by using HSA, PSA and PSA as selectors, respectively. The chiral recognition ability of HSA and PSA was compared. HSA and PSA show a different chiral recognition ability for each of the three drugs. In addition, the association constants between enantiomeric drugs and proteins were determined to be 2.00 and 3.80 × 10 2 M -1 for mexiletine and HSA, 0.59 and 1.12 × 10 3 M -1 for chlorpheniramine and PSA, and 0.87 and 1.42 × 10 3 M -1 for propranolol and PSA. The method for the chiral separation and determination of association constants possesses the advantages of simple performance, effective avoiding of the interference of the UV detection from protein, and lowering of the reagent consumption.

Recent developments in capillary electrophoresis and capillary electrochromatography of peptides

“…Binding constants between macrocyclic antibiotics receptors and peptide ligands can be determined also by dual-marker form of CAE [132]. The principle of affinity biorecognition is utilized also for enantiomeric separations by CAE using proteins and peptides as free or immobilized chiral selectors [133,134].…”

Chiral resolution of tryptophan derivatives by CE using canine serum albumin and bovine serum albumin as chiral selectors

“…As in HPLC, the retention and enantioselectivity can be influenced in CE also by the pH [51][52][53]. A change of pH causes a modification of the electrostatic analyte-protein interactions because of a change in their net charges [54].…”

Recent developments of enantioseparation techniques for adrenergic drugs using liquid chromatography and capillary electrophoresis: A review

“…Xu and Yu [134] separated propranolol with HSA and porcine serum albumin by CE in combination with the partial filling technique, and Martínez-Pla et al [135] described a simple and fast method for enantiomeric resolution of the same drug by ACE using HSA as chiral selector, the effect of several experimental variables such as HSA concentration, temperature, chiral selector plug length and addition of organic modifiers (1-propranol), on the separation was evaluated. Martínez-Gómez's group [136,137] dealt with four adrenergic enantiomers by AEKC-partial filling technique using HSA; protein concentration, running pH and protein solution plug length were optimized.…”