Enantioseparation of racecadotril using polysaccharide-type chiral stationary phases in polar organic mode

Zoltán István Szabó, Mohammadhassan Foroughbakhshfasaei, B. Noszál, Gergő Tóth

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Enantioseparation of the antidiarrheal drug, racecadotril, was investigated by liquid chromatography using polysaccharide-type chiral stationary phases in polar organic mode. The enantiodiscrimininating properties of 4 different chiral columns (Chiralpak AD, Chiralcel OD, Chiralpak AS, Chiralcel OJ) with 5 different solvents (methanol, ethanol, 1-propanol, 2-propanol, and acetonitrile) at 5 different temperatures (5–40 °C) were investigated. Apart from Chiralpak AS column the other 3 columns showed significant enantioseparation capabilities. Among the tested mobile phases, alcohol type solvents were superior over acetonitrile, and significant differences in enantioselective performance of the selector were observed depending on the type of alcohol employed. Van't Hoff analysis was used for calculation of thermodynamic parameters which revealed that enantioseparation is mainly enthalpy controlled; however, enthropic control was also observed. Enantiopure standard was used to determine the enantiomer elution order, revealing chiral selector—and mobile-phase dependent reversal of enantiomer elution order. Using the optimized method (Chiralcel OJ stationary phase, thermostated at 10 °C, 100% methanol, flow rate: 0.6 mL/min) baseline separation of racecadotril enantiomers (resolution = 3.00 ± 0.02) was achieved, with the R-enantiomer eluting first. The method was validated according to the ICH guidelines, and its application was tested on capsule and granules containing the racemic mixture of the drug.

Original languageEnglish
Pages (from-to)95-105
Number of pages11
JournalChirality
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Enantiomers
Polysaccharides
Methanol
Alcohols
Antidiarrheals
1-Propanol
2-Propanol
Propanol
Acetonitrile
Thermodynamics
Liquid Chromatography
Capsules
Ethanol
Guidelines
Temperature
Liquid chromatography
Pharmaceutical Preparations
Enthalpy
Flow rate
racecadotril

Keywords

  • chiral separation
  • elution order
  • HPLC
  • sinorphan
  • van't Hoff analysis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Cite this

Enantioseparation of racecadotril using polysaccharide-type chiral stationary phases in polar organic mode. / Szabó, Zoltán István; Foroughbakhshfasaei, Mohammadhassan; Noszál, B.; Tóth, Gergő.

In: Chirality, Vol. 30, No. 1, 01.01.2018, p. 95-105.

Research output: Contribution to journalArticle

Szabó, Zoltán István ; Foroughbakhshfasaei, Mohammadhassan ; Noszál, B. ; Tóth, Gergő. / Enantioseparation of racecadotril using polysaccharide-type chiral stationary phases in polar organic mode. In: Chirality. 2018 ; Vol. 30, No. 1. pp. 95-105.
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