The sodium salt of the enantiomers of ricobendazole: Preparation, solubility and chiroptical properties

Roberto Cirilli, Paolo Guglielmi, Francesca Romana Formica, Adriano Casulli, Simone Carradori

Research output: Contribution to journalArticle

Abstract

Albendazole (ABZ) is a sulfanyl-benzimidazole anthelmintic drug used worldwide in the treatment and prevention of parasitic diseases in animals and humans. Following oral administration, ABZ is rapidly oxidized into the pharmacologically active chiral sulfoxide metabolite known as ricobendazole (RBZ). As its achiral precursor, RBZ shows very low intestinal absorption due to its poor solubility in water (0.06 mg mL−1). To the best of our knowledge, there is no known example in human medicine of a water-soluble salt form of racemic or enantiomerically pure RBZ. In the present study, we describe in detail the preparation of the sodium (Na) salt of the enantiomers of RBZ through a two-step process: i) the multi-milligram resolution of RBZ by HPLC on the amylose-based Chiralpak IG chiral stationary phase under polar organic mode; ii) the salification of the isolated enantiomers of RBZ by reaction with sodium hydroxide solution. The spectroscopic and chiroptical properties of the RBZ-Na enantiomers were determined. Due to their unique solubility in 0.01 M phosphate buffer at physiological pH (14.49 mg mL−1) and the high sample throughput obtained on semipreparative separation of the non-salified form, it is potentially possible to develop new anthelmintic enantiopure formulations with improved pharmacokinetic properties and lower toxicity.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume139
DOIs
Publication statusPublished - May 30 2017

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Keywords

  • Chiralpak IG
  • Enantiomers
  • Neglected tropical diseases
  • Ricobendazole sodium salt
  • Semipreparative resolution
  • Water solubility

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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