Chiral resolution of the enantiomers of new selective CB(2) receptor agonists by liquid chromatography on amylose stationary phases

J Pharm Biomed Anal. 2008 Apr 14;46(5):848-53. doi: 10.1016/j.jpba.2007.01.044. Epub 2007 Feb 3.

Abstract

Analytical HPLC methods using derivatized amylose chiral stationary phases, Chiralpak AD-H and Chiralpak AS, were developed for the direct enantioseparation of eight substituted 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives with one stereogenic center. Baseline separation (Rs>1.5) was always achieved on amylose based Chiralpak AD-H column to the difference with Chiralpak AS. Using UV detection, a linear response was observed within a 180-420 micromol L(-1) concentration range (r2>0.991) for three racemic compounds 1, 3 and 4 with best pharmacological potentials; repeatability, limit of detection (LD) and quantification (LQ) were also determined: LD varied, for the solutes, from 0.36 to 2.56 micromol L(-1). Finally, the enantiopurity of these compounds was determined. Additionally, the effect of temperature variations upon isomer separations was investigated.

MeSH terms

  • Amylose / analogs & derivatives*
  • Amylose / chemistry
  • Carbamates / chemistry*
  • Chromatography, High Pressure Liquid* / standards
  • Molecular Structure
  • Phenylcarbamates / chemistry*
  • Quinolines / chemistry
  • Quinolines / isolation & purification*
  • Quinolines / pharmacology
  • Receptor, Cannabinoid, CB2 / agonists*
  • Reproducibility of Results
  • Solvents / chemistry
  • Spectrophotometry, Ultraviolet
  • Stereoisomerism
  • Technology, Pharmaceutical / methods*
  • Technology, Pharmaceutical / standards
  • Temperature

Substances

  • Carbamates
  • Phenylcarbamates
  • Quinolines
  • Receptor, Cannabinoid, CB2
  • Solvents
  • chiralpak AS
  • Chiralpak AD
  • Amylose