Effects of the substitution degree and position of hydroxypropyl-β-cyclodextrin on chiral separation of drugs by capillary electrophoresis

Several hydroxypropyl-beta-cyclodextrins (HP-beta-CDs) with various degree of substitution and different position of substitution were synthesized. The average degree of substitution (D-S) of HP-beta-CD were determined by fast atom bombardment mass spectrometry (FAB-MS). The effects of the D-S of HP-beta-CD on CE resolution of four basic drugs were studied. The results show that D-S has a different effects on the separation of various drugs because of different molecular structures. At D-S=0 (beta-CD), no separation was found for isoproterenol, ofloxacin and propranolol. The resolution of both isoproterenol and ofloxacin increased with the increase of D-S, but decreased when D-S was 14. The best resolution was at D-S=10.2. The resolution of propranolol increased with increasing D-S. In contrast, the resolution of chlorophiramine decreased with the increase of D-S. The effects of the position of substitution of HP-beta-CD on separations were also investigated. The results demonstrate that the substitution at the second position of CD plays an important role in the separation of enantiomers. In general, the more substitution at the second position of CD, the better the separation was obtained because the substitution of the second position made the wide opening become wider. This probably makes it easier for some molecular to enter the cyclodextrin cavity, which could facilitate enantiomeric separation.