Enantiomeric separation of the antiuremic drug colchicine by electrokinetic chromatography. Method development and
Nuria Menéndez-López1, Jesús Valimaña-Traverso1, María Castro-Puyana1
1Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, 28871 Madrid, Spain.
Abstract:
Two analytical methodologies were developed by CE enabling the enantiomeric separation of colchicine, an antiuremic drug commercialized as pure enantiomer. Succinyl-γ-CD and Sulfated-γ-CD were selected as chiral selectors after a screening with different anionic CDs. Under the optimized conditions, chiral resolutions of 5.6 in 12min and 3.2 in 8min were obtained for colchicine with Succinyl-γ-CD and Sulfated-γ-CD, respectively. An opposite enantiomeric migration order was observed with these two CDs being S-colchicine the first-migrating enantiomer with Succinyl-γ-CD and the second-migrating enantiomer with Sulfated-γ-CD. H NMR experiments showed a 1:1 stoichiometry for the enantiomer-CD complexes in both cases. However, the apparent and averaged equilibrium constants for the enantiomer-CD complexes could be calculated only for Succinyl-γ-CD. The developed methods were applied to the analysis of pharmaceutical formulations but only the use of Succinyl-γ-CD enabled to detect a 0.1% of enantiomeric impurity in colchicine formulations.
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