Separation of enantiomers of butorphanol and cycloamine by capillary zone electrophoresis.

Butorphanol tartrate is a synthetic opioid agonist-antagonist used as analgesic, possessing three chiral centres in the basic part of the molecule. Its chiral purity is routinely controlled only by optical rotation. A new capillary zone electrophoresis method, capable to separate the enantiomers of butorphanol and intermediate of its synthesis, cycloamine, was developed. Different electrolyte composition (type and concentration of carrier ion, pH, and organic solvent addition), and type and concentration of several chiral selectors (natural and modified cyclodextrins) were tested. Using the optimized conditions (acidic electrolyte with the addition of highly sulphated gamma-cyclodextrin) as low as 0.05% of undesirable enantiomers can be detected. Selected method characteristics, i.e., linearity (0-50 mg/l), precision (2.5% at 20 mg/l), and accuracy (101 +/- 2% at 20 mg/l) were evaluated. The optimized method was applied for the analysis of real batches of butorphanol and cycloamine. It was found that butorphanol tartrate manufactured by IVAX Pharmaceuticals contains less than 0.05% of undesirable enantiomer.

Capillary zone electrophoresis separation of enantiomers of lisuride.

Lisuride is an ergot alkaloid derivative with dopaminergic activity. It is used for treatment of Parkinsonism and some other diseases associated with high level of prolactine. Lisuride is a chiral compound derived from natural ergot alkaloids. A new capillary zone electrophoresis (CZE) method capable of separating the enantiomers of lisuride was developed. Using the optimized conditions (acidic electrolyte with the addition of gamma-cyclodextrin (gamma-CD)) as low as 0.02% of undesirable L-lisuride can be detected. Selected method characteristics, i.e., linearity (0-20 mg/l), precision (2.0% at 5 mg/I), and accuracy (101 +/- 4% at 5 mg/l) were evaluated. The optimized method was applied for the analysis of real batches of Lisuride hydrogenmaleate and Lisuride base manufactured by IVAX Pharmaceuticals. It was found that they contain less than 0.02% of undesirable L-enantiomer.