Affiliation:
1. Determinants of Aging‐Related Diseases, Inserm U1167‐Risk Factors and Molecular Université de Lille Lille France
2. Alexandru Ioan Cuza University of Iasi Faculty of Chemistry Iasi Romania
3. Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium
4. Department of Toxicology, Faculty of Pharmacy Medical University of Gdańsk Gdańsk Poland
Abstract
AbstractIn this work, a preparative supercritical fluid chromatography (SFC) method was first developed to separate a series of chiral compounds evaluated as lactam‐based P2RX7 antagonists. Subsequently, high‐performance liquid chromatography, SFC, and capillary electrophoresis (CE) were comparatively investigated as QC tools to determine the enantiomeric purity of the separated isomers, including analytical performance and greenness. The screening of the best conditions was carried out in liquid and SFC on the nine derivatives and the amylosetris(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase was found to be highly efficient. The same screening was carried out in CE and very different conditions, either in acidic or basic background electrolyte and different cyclodextrins used as chiral selectors, allowed the separation of six of the nine derivatives. 1‐((3,4‐Dichlorophenyl)carbamoyl)‐5‐oxopyrrolidine‐2‐carboxylic acid (compound1) was chosen as a probe, and its semi‐preparative separation by SFC and enantiomeric verification using the three techniques are presented. Its limit of detection and limit of quantification are calculated for each method. Finally, the greenness of each quality control method was evaluated.
Subject
Clinical Biochemistry,Biochemistry,Analytical Chemistry