Simultaneous enantioselective separation of azelastine and three of its metabolites for the investigation of the enantiomeric metabolism in rats. I. Liquid chromatography-ionspray tandem mass spectrometry and electrokinetic capillary chromatography

J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Aug 15;793(2):389-404. doi: 10.1016/s1570-0232(03)00357-x.


Enantioselective separation methods and the enantioselective determination of the anti-allergic drug azelastine and of three of its main phase I metabolites in a biological matrix underwent chromatographic and electrophoretic investigations. An enantioselective assay of a coupling of HPLC using a beta-cyclodextrin chiral stationary phase to ionspray tandem mass spectrometry is presented. Additionally, this assay is compared to another enantioselective assay using electrokinetic capillary chromatography with beta-cyclodextrin and carboxymethyl-beta-cyclodextrin in polyacrylamide-coated capillaries. For capillary electrophoresis (CE) the importance of polyacrylamide coating for the validation of this separation method is highlighted. Extracted rat plasma samples of enantioselective metabolism studies were measured by both validated assays. Differences in the pharmacokinetics and pharmacodynamics were evaluated for the main substance azelastine and its main metabolite demethylazelastine. So, a first hint about the enantioselectivity of biotransformation of azelastine in rats was seen after oral application of either enantiomer or the racemate to rats.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, Micellar Electrokinetic Capillary / methods*
  • Histamine H1 Antagonists / isolation & purification*
  • Histamine H1 Antagonists / metabolism
  • Histamine H1 Antagonists / pharmacokinetics
  • Male
  • Phthalazines / isolation & purification*
  • Phthalazines / metabolism
  • Phthalazines / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Stereoisomerism


  • Histamine H1 Antagonists
  • Phthalazines
  • azelastine