FRACTIONATION AND CHARACTERIZATION OF 4-SULFOBUTYL ETHER DERIVATIVES OF CYCLOMALTOHEPTAOSE (BETA-CYCLODEXTRIN)

4-Sulfobutyl ether derivatives of cyclomaltoheptaose (beta-cyclodextri n) (SBE-beta-CD) are being developed as parenterally safe solubilizing and stabilizing agents. SBE-beta-CDs are a mixture of positional and regional isomers containing from one to as many as twelve sulfobutyl e ther (SEE) groups per cyclodextrin. Capillary electrophoretic (CE) ana lysis of these mixtures resolves these isomers based on the molar degr ee of SEE substitution (ds), and the electropherogram shows an almost symmetrical distribution of SEE incorporation centered around the band which represents the apparent average degree of substitution for the mixture. The objectives of this study were to isolate the different su bstitution bands for their characterization and to evaluate their mass contribution to the mixture. Mixtures of SBE-beta-CDs containing from mono- up to deca-SBE substitutions were fractionated by preparative a nion-exchange chromatography with salt concentration gradient elution. The bands for each ds were well resolved as characterized by CE analy sis with indirect UV detection. The isolated materials were desalted a nd lyophilized to obtain white solids, which were then characterized b y nuclear magnetic resonance (H-1 NMR) spectroscopy, capillary electro phoresis (CE), and fast-atom-bombardment mass spectrometry (FABMS). Th e CE molar response factor of each ds was then determined, and the act ual percent mass composition of a SBE-beta-CD mixture was calculated. (C) 1997 Elsevier Science Ltd.