Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits

Chirality. 2020 Aug;32(8):1091-1106. doi: 10.1002/chir.23241. Epub 2020 Jun 21.

Abstract

Enantiomeric resolution and molecular docking studies of meclizine hydrochloride on polysaccharide-based chiral stationary phase comprising cellulose tris(4-methylbenzoate) chiral selector (150 × 4.6 mm, 3.0 μm) were presented. The mobile phase used was acetonitrile:10mM ammonium bicarbonate (95:05, v/v). The developed technique was used to perform the enantioselective assay of meclizine hydrochloride in its marketed formulation. The elution order of meclizine hydrochloride enantiomers was determined by docking studies. Target compound was extracted from rabbit plasma using protein precipitation technique, followed by development of bioanalytical chiral separation method using the same matrix. Application of the method to determine pharmacokinetic parameters of meclizine hydrochloride enantiomers was performed using Phoenix WinNonlin 8.1 software. The results demonstrated stereoselective disposition of meclizine hydrochloride enantiomers in rabbits.

Keywords: bioanalytical; chiral; docking; meclizine hydrochloride; pharmacokinetics.

MeSH terms

  • Animals
  • Drug Compounding
  • Meclizine / chemistry*
  • Meclizine / isolation & purification
  • Meclizine / pharmacokinetics*
  • Molecular Docking Simulation*
  • Rabbits
  • Stereoisomerism
  • Tissue Distribution

Substances

  • Meclizine