Electrophoretic chiral separation of pharmaceutical compounds with multiple stereogenic centers in charged cyclodextrin media

Abstract

This paper reports the use of sulfated β-Cyclodextrins (S-β-CDs) (degree of substitution (DS) = 7–11 and 15), hepta-6-sulfato-β-CD (HS-β-CD), heptakis (2,3-dimethyl-6-sulfato)-β-CD (HDMS-β-CD), and heptakis (2,3-diacetyl-6-sulfato)-β-CD (HDAS-β-CD) in conjunction with capillary zone electrophoresis (CZE) to separate enantiomers of several commercially available pharmaceutical compounds with multiple stereogenic centers. Compounds studied include eucatropine, fenoterol, nadolol, nafronyl, nylidrin, and pentapiperide. S-β-CD with a relatively high degree of substitution is shown to be effective in separating several of these compounds due to the high selectivity. Resolution of four isomers was achieved for several of the test compounds under counter-electroosmotic flow (EOF) conditions in less than ten minutes. Data illustrating the effects of CD concentration and pH are presented. It is also shown that the migration order of isomers can be manipulated by changing either the CD concentration or buffer pH.