Human Serum Albumin as Chiral Selector in Enantioselective High-Performance Liquid Chromatography

Curr Med Chem. 2017;24(8):743-757. doi: 10.2174/0929867324666161118115711.

Abstract

Enantioselective high-performance liquid chromatography (eHPLC) using chiral stationary phases (CSPs) is surely the most used technique for the determination of the enantiomeric excess (e.e.) of chiral drugs, a fundamental parameter for reliable studies on the relationship between stereochemistry and pharmacological activity. A key aspect of this enantioseparation technique is the efficiency of the chiral selector, which can be optimized to obtain higher selectivity and a wider applicability. Thus, the determination of the mechanisms behind chiral recognition is very important to predict and improve the enantioselectivity of CSPs. The present review deals with the preparation and use of CSPs for eHPLC with human serum albumin (HSA) as chiral selector, with particular emphasis on the modulation of the chromatographic performance. HSA-based CSPs allow a relatively easy prediction of the binding sites involved in the retention of analytes and the possibility to improve the selectivity of enantioresolution by modulating the binding process, using either reversible or covalent modifications of the protein. Significant improvements of the chromatographic parameters, such as reduction of analysis time and increase of enantioselectivity, have been obtained for selected analytes by using competitors for a particular binding site of HSA dissolved in the mobile phase or by selectively modifying the protein structure at single amino acid residues.

Keywords: Enantioselective HPLC; chiral discrimination; drugs; enantioselectivity modulation; human serum albumin; protein-based chiral stationary phases.

Publication types

  • Review

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Serum Albumin / chemistry*
  • Stereoisomerism

Substances

  • Serum Albumin