Affordable Access

deepdyve-link
Publisher Website

Enantiomeric separation of ivabradine by cyclodextrin-electrokinetic chromatography. Effect of amino acid chiral ionic liquids.

Authors
  • Casado, Natalia1
  • Salgado, Antonio2
  • Castro-Puyana, María3
  • García, María Ángeles3
  • Marina, María Luisa4
  • 1 Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain. , (Spain)
  • 2 Centro de Espectroscopía de Resonancia Magnética Nuclear (CERMN), Centro de Apoyo a la Investigación en Química (CAIQ), Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain. , (Spain)
  • 3 Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain; Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain. , (Spain)
  • 4 Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain; Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain. Electronic address: [email protected] , (Spain)
Type
Published Article
Journal
Journal of chromatography. A
Publication Date
Dec 20, 2019
Volume
1608
Pages
460407–460407
Identifiers
DOI: 10.1016/j.chroma.2019.460407
PMID: 31383356
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A chiral methodology was developed for the first time to ensure the quality control of ivabradine, a novel anti-ischemic and heart rate lowering drug commercialized as a pure enantiomer. With this aim, electrokinetic chromatography (EKC) was employed and the enantiomeric separation of ivabradine was investigated using different anionic and neutral cyclodextrins (CDs) and amino acid-based chiral ionic liquids (CILs) as sole chiral selectors. Baseline separation was only achieved with sulfated CDs, and the best enantiomeric resolution was obtained with sulfated-γ-CD. Under the optimized conditions, ivabradine enantiomers were separated in 6 min with a resolution of 2.7. Nuclear magnetic resonance experiments showed a 1:1 stoichiometry for the enantiomer-CD complexes and apparent and averaged equilibrium constants were determined. The combined use of sulfated-γ-CD and different CILs as dual separation systems was investigated, resulting in a significant increase in the resolution. The use of 5 mM tetrabutylammonium-aspartic acid ([TBA][L-Asp]) in 50 mM formate buffer (pH 2.0) containing 4 mM sulfated-γ-CD were considered the best conditions in terms of resolution and migration times for ivabradine enantiomers. Nevertheless, as no inversion of the enantiomer migration order was observed when combining CILs and sulfated-γ-CD and a good enantiomeric resolution and efficiency were obtained using just sulfated-γ-CD as the sole chiral selector, the analytical characteristics of this method were evaluated, showing good recovery (98% and 103% for S- and R-ivabradine, respectively) and precision values (RSD < 5% for instrumental repeatability, < 6% for method repeatability and < 7% for intermediate precision). The limits of detection (LODs) were 0.22 and 0.28 μg mL-1 for S- and R-ivabradine, respectively, and the method enabled to detect a 0.1% of the enantiomeric impurity, allowing to accomplish the requirements of the International Conference on Harmonisation (ICH) guidelines. Finally, the method was applied to the analysis of a pharmaceutical formulation of ivabradine. The content of R-ivabradine was below the LOD and the amount of S-ivabradine was in agreement to the labeled content. Copyright © 2019 Elsevier B.V. All rights reserved.

Report this publication

Statistics

Seen <100 times