Resolution of ephedrine derivatives by means of neutral and sulfated heptakis(2,3-di-O-acetyl)beta-cyclodextrins using capillary electrophoresis and nuclear magnetic resonance spectroscopy.
Beta-cyclodextrin (beta-CD), heptakis(2,3-di-O-acetyl)beta-cyclodextrin (Diac-beta-CD) and heptakis (2,3-di-O-acetyl-6-sulfato)beta-cyclodextrin (HDAS-beta-CD) were tested for their ability to discriminate the enantiomers of ephedrine, pseudoephedrine, norephedrine and methylephedrine. Using capillary electrophoresis (CE) under optimized conditions, with the exception of norephedrine in presence of beta-CD, all racemates could be resolved. Utilizing Job's plot by means of UV spectroscopy revealed 1:1 complexes formed with beta-CD and Diac-beta-CD. HDAS-beta-CD gave curved plots indicating mixed stoichiometry. Inspection of the cyclodextrin-induced chemical shifts (CICS) of both the ligands and the CDs showed that the ephedrine sits deeply in the cavity of beta-CD and HDAS-beta-CD. In the case of Diac-beta-CD, the ephedrine is located closely to the wider rim of the CD cavity. In conclusion, comparing the pattern of CICS of the various CD derivatives clearly indicates the differences in the complex geometry.
Wedig
M
M
Pharmaceutical Institute, University of Würzburg, Germany.
Holzgrabe
U
U
D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D004809:Ephedrine / Q000031:analogs & derivatives / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C092855:heptakis(2,3-di-O-acetyl)beta-cyclodextrin; D004809:Ephedrine