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, B. Noszál, Pavel Dubský, Gergő Tóth

Research output: Contribution to journalArticle

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
JournalElectrophoresis
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Rabeprazole
Lansoprazole
Capillary electrophoresis
Cyclodextrins
Capillary Electrophoresis
Ether
Enantiomers
Dexlansoprazole
Buffers
Substitution reactions
Phosphates
Injections
Temperature
Proton Pump Inhibitors
Electric potential
Design of experiments
Screening
Research Design
Guidelines
Impurities

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems. / Papp, Lajos Attila; Hancu, Gabriel; Gyéresi, Árpád; Kelemen, Hajnal; Szabó, Zoltán István; Noszál, B.; Dubský, Pavel; Tóth, Gergő.

In: Electrophoresis, 01.01.2019.

Research output: Contribution to journalArticle

Papp, Lajos Attila ; Hancu, Gabriel ; Gyéresi, Árpád ; Kelemen, Hajnal ; Szabó, Zoltán István ; Noszál, B. ; Dubský, Pavel ; Tóth, Gergő. / Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems. In: Electrophoresis. 2019.
@article{71982df9f357459bba0fd8995b464065,
title = "Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems",
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.",
keywords = "Chiral separation, Dual cyclodextrin system, Experimental design, Lansoprazole, Rabeprazole",
author = "Papp, {Lajos Attila} and Gabriel Hancu and {\'A}rp{\'a}d Gy{\'e}resi and Hajnal Kelemen and Szab{\'o}, {Zolt{\'a}n Istv{\'a}n} and B. Nosz{\'a}l and Pavel Dubsk{\'y} and Gergő T{\'o}th",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/elps.201900107",
language = "English",
journal = "Electrophoresis",
issn = "0173-0835",
publisher = "Wiley-VCH Verlag",

}

TY - JOUR

T1 - Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems

AU - Papp, Lajos Attila

AU - Hancu, Gabriel

AU - Gyéresi, Árpád

AU - Kelemen, Hajnal

AU - Szabó, Zoltán István

AU - Noszál, B.

AU - Dubský, Pavel

AU - Tóth, Gergő

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Chiral separation

KW - Dual cyclodextrin system

KW - Experimental design

KW - Lansoprazole

KW - Rabeprazole

UR - http://www.scopus.com/inward/record.url?scp=85069910756&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069910756&partnerID=8YFLogxK

U2 - 10.1002/elps.201900107

DO - 10.1002/elps.201900107

M3 - Article

C2 - 31281995

AN - SCOPUS:85069910756

JO - Electrophoresis

JF - Electrophoresis

SN - 0173-0835

ER -