Enantioseparation of some antimicotic drugs using polysaccharide-based chiral selectors with polar-organic and reversed mobile phasesin high-performance liquid chromatography

Author: Marina Karchkhadze
Co-authors: Antonina Mskhiladze2, Lali Chankvetadze1, Bezhan Chankvetadze 1
Keywords: high-performance liquid chromatography, polysaccharide-based chiral selectors, separation of enantiomers, enantiomer elution order, antimycotic chiral drugs.
Annotation:

1- Department of Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Chavchavadze Ave 3, 0179 Tbilisi, Georgia 2- Faculty of Natural Sciences and Healthcare, Sokhumi State University, Polytkovskaya 9, 0186, Tbilisi, Georgia Enantioseparation of 8 chiral antimycotic drugs was studied using polysaccharide-based chiral selectors with polar-organic and reversed mobile phases in high-performance liquid chromatography. Antimycotic drugs studied are diazole and triazole derivatives. 5 cellulose- and 2 amylose-based chiral selectors were used for the presentstudy. The effect of structure of chiral selector and mobile phase composition onenantioselectivity was established. Addition of ammonium acetate to mobile phase increased the enantioselectivity and generally caused dicrease of retention time. Addition of water in case of methanol as a mobile phase increased retention times, but with acetonitrile the trend was different: small amountsof water decreased retention times firstly but after increasing the percentage of water in mobile phase over 20% (v/v), values of retention times were increased.All 4 stereoisomers of itraconazolewere separated using Cellulose-4 columnwith 3 % water content in mobile phase, but was not separated using Cellulose-2column with the same mobile phase.Baseline separation of ornidazole enantiomers was observedon Cellulose-2 column while only partial enantioseparationwas observed on Cellulose-4 column. Also, adding of water to mobile phase worsened enantioselectivity in both cases. The enantiomers of ornidazole were not separated at all using chiral selectors Cellulose tris(3,4-dichlorophenylcarbamate) and Cellulose tris(3,4-dimethylphenylcarbamate).Reversal of enantiomer elution order was observed forsulconazole by changing the chiral selector from cellulosetris(3,5-diclorphenylcarbamate) to cellulosetris(2,5-diclorphenylcarbamate).