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

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.

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri‐(3,5‐dimethylphenycarbamate) column (Chiralcel OD‐RH) and its recognition mechanisms

“…A pair of antihistamine enantiomers could have different biological activities and pharmacological profiles. For example, the disparate pharmacokinetic properties of meclizine enantiomers have been demonstrated that the drug concentration of R ‐meclizine was found to be higher than S ‐meclizine in the rabbits, and significant variation in the stereo‐specific disposition of the meclizine enantiomers is marked with an obvious difference in most of the pharmacokinetic parameters between the two enantiomers [9]. Orphenadrine was proven to show stereoselectivity in binding to the human serum albumin [10,11].…”