INFLUENCE OF CHROMATOGRAPHIC DESCRIPTORS ON ENANTIORESOLUTION OF A DIHYDROPYRIDINE AND STRUCTURALLY RELATED-COMPOUNDS

The possibility to separate the enantiomers of a pharmacological activ e dihydropyridine and some of its possible by-products/metabolites was mapped using experimental design and multivariate analysis. All the t ested racemates were enantioseparated using Chiral-AGP as the chiral s tationary phase. All the investigated descriptor variables, mobile pha se pH, organic modifier(s) and column temperature influenced the chira l recognition. The separation factor of the aprotic compound of pharma cological interest, H 324/38 (Solute No. 1), increased by increasing m obile phase pH, indicating changes in the conformation of the immobili zed protein. The enantiomers of the major compound, a potential intern al standard and the most important degradation product as well as the major metabolite, H 152/81 (Solute No. 5), could be separated simultan eously using a mix of two organic modifiers in the mobile phase. The p resented work emphasises the use of experimental design and statistica l multivariate evaluation. However, knowledge about the chromatographi c system and the physical properties of the analytes, e.g., pK(a) valu es, are of highest importance in order to derive accurate conclusions.