Effect of various cyclodextrin derivatives on the resolution of fencamfamine isomers with capillary electrophoresis and nuclear magnetic resonance

• Published in: Journal of Chromatography A 1998-09, Vol.818 (2), p.239-249
• Main Authors: Thunhorst, Martin, Otte, Yvonne, Jefferies, Terry M, Branch, Sarah K, Holzgrabe, Ulrike
• Format: Article
• Language: English
• Subjects: Analysis; Biological and medical sciences; Cyclodextrins; Fencamfamine; General pharmacology; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0021-9673
• DOI: 10.1016/S0021-9673(98)00562-7

Even though it is known that the enantiomers of a drug can exhibit different pharmacokinetic and dynamic properties, fencamfamine has been used in clinical practice as a mixture of four isomers, arising from the two centres of chirality in the molecule. The purpose of this investigation was to establish a capillary electrophoretic method for the discrimination of the isomers of fencamfamine and to determine its isomeric composition. The chiral selectors studied were uncharged α-cyclodextrin (α-CD), β-CD, heptakis(2,3-di- O-acetyl)β-cyclodextrin, γ-CD and octakis(2,3-di- O-acetyl)γ-cyclodextrin, and the negatively charged sulfobutylether-β-CD. In order to optimize the separation conditions, the selector concentration, pH values and buffer strength were varied. With Diac-β-CD and γ-CD, a very high resolution of the four isomers was found. Interestingly, the migration order of the diastereomers was different for these two selectors. In each case NMR spectroscopic studies revealed multiple isomer–cyclodextrin complexes to be responsible for the good discrimination of the isomers. In contrast to the classical inclusion complexes mostly described for CDs, fencamfamine was found to interact mainly with the outside region of the CD cavity.