Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems

Lajos Attila Papp, Gabriel Hancu, Árpád Gyéresi, Hajnal Kelemen, Zoltán István Szabó, Béla Noszál, Pavel Dubský, Gergő Tóth

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Abstract

Novel capillary electrophoresis methods using CDs as chiral selectors were developed and validated for the chiral separation of lansoprazole and rabeprazole, two proton pump inhibitors. Fourteen different neutral and anionic CDs were screened at pH 4 and 7 in the preliminary analysis. Sulfobutyl-ether-β-CD with a degree of substitution of 6.5 and 10 at neutral pH proved to be the most suitable chiral selector for both compounds. Various dual CD systems were also compared, and the possible mechanisms of enantiomer separation were investigated. A dual selector system containing sulfobutyl-ether-β-CD degree of substitution 6.5 and native γ-CD proved to be the most adequate system for the separations. Method optimization was carried out using an experimental design approach, performing an initial fractional factorial screening design, followed by a central composite design to establish the optimal analytical conditions. The optimized methods (25 mM phosphate buffer, pH 7, 10 mM sulfobutyl-ether-β-CD/20 mM γ-CD, +20 kV voltage; 17°C temperature; 50 mbar/3 s injection, detection at 210 nm for lansoprazole; 25 mM phosphate buffer, pH 7, 15 mM sulfobutyl-ether-β-CD/30 mM γ-CD, +20 kV voltage; 18°C temperature; 50 mbar/3 s injection, detection at 210 nm for rabeprazole) provided baseline separation for lansoprazole (Rs = 2.91) and rabeprazole (Rs = 2.53) enantiomers with favorable migration order (in both cases the S-enantiomers migrates first). The optimized methods were validated according to current guidelines and proved to be reliable, linear, precise, and accurate for the determination of 0.15% distomer as chiral impurity in dexlansoprazole and dexrabeprazole samples.

Original languageEnglish
Pages (from-to)2799-2805
Number of pages7
JournalELECTROPHORESIS
Volume40
Issue number21
DOIs
Publication statusPublished - Nov 1 2019

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Keywords

  • Chiral separation
  • Dual cyclodextrin system
  • Experimental design
  • Lansoprazole
  • Rabeprazole

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry

Cite this

Papp, L. A., Hancu, G., Gyéresi, Á., Kelemen, H., Szabó, Z. I., Noszál, B., Dubský, P., & Tóth, G. (2019). Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems. ELECTROPHORESIS, 40(21), 2799-2805. https://doi.org/10.1002/elps.201900107