Enantiomer separations by nonaqueous capillary electrophoresis using octakis(2,3-diacetyl-6-sulfato)-γ-cyclodextrin

Abstract

The newest member of the single-isomer isomer sulfated cyclodextrin family, octakis(2,3-diacetyl-6-sulfato)-γ-cyclodextrin (ODAS-γ-CD) was used for the first time as a resolving agent for the nonaqueous capillary electrophoretic separation of the enantiomers of 26 weak base pharmaceuticals in an acidic methanol background electrolyte. The solubility limit of ODAS-γ-CD at room temperature proved to be 55 m M in this background electrolyte, which afforded good, fast enantiomer separations for most of the basic drugs tested. For all the bases studied, the effective mobilities and separation selectivities were found to follow the predictions of the charged resolving agent migration model of electrophoretic enantiomer separations. The effective mobilities of the weakly binding weak bases remained cationic throughout the entire 0 to 45 m M ODAS-γ-CD concentration range; separation selectivities increased as the ODAS-γ-CD concentration was increased. The effective mobilities of the moderately binding weak bases became anionic in the 2.5 to 45 m M ODAS-γ-CD concentration range; separation selectivities first increased as the effective mobilities approached zero, then decreased again as the ODAS-γ-CD concentration was increased further. The effective mobilities of the strongly binding weak bases became anionic in the 0 to 2.5 m M ODAS-γ-CD concentration range; separation selectivities decreased as the ODAS-γ-CD concentration was increased above 2.5 m M.