EFFECT OF VARIOUS CYCLODEXTRIN DERIVATIVES ON THE RESOLUTION OF FENCAMFAMINE ISOMERS WITH CAPILLARY-ELECTROPHORESIS AND NUCLEAR-MAGNETIC-RESONANCE

Even though it is known that the enantiomers of a drug can exhibit dif ferent pharmacokinetic and dynamic properties, fencamfamine has been u sed in clinical practice as a mixture of four isomers, arising from th e two centres of chirality in the molecule. The purpose of this invest igation was to establish a capillary electrophoretic method for the di scrimination of the isomers of fencamfamine and to determine its isome ric composition. The chiral selectors studied were uncharged alpha-cyc lodextrin (alpha-CD), beta-CD, heptakis(2,3-di-O-acetyl)beta-cyclodext rin, gamma-CD and octakis(2,3-di-O-acetyl)gamma-cyclodextrin, and the negatively charged sulfobutylether-beta-CD. In order to optimize the s eparation conditions, the selector concentration, pH values and buffer strength were varied. With Diac-beta-CD and gamma-CD, a very high res olution of the four isomers was found. Interestingly, the migration or der of the diastereomers was different for these two selectors. In eac h case NMR spectroscopic studies revealed multiple isomer-cyclodextrin complexes to be responsible for the good discrimination of the isomer s. In contrast to the classical inclusion complexes mostly described f or CDs, fencamfamine was found to interact mainly with the outside reg ion of the CD cavity. (C) 1998 Elsevier Science B.V. All rights reserv ed.