Optimisation of Chiral Separation of Doxazosin Enantiomers by High-Performance Liquid Chromatography on a Second Generation α₁-Acid Glycoprotein Column

Summary

The separation of the enantiomers of doxazosin (1-(4-amino-6,7-dimethyoxy-2quinazolinyl)-4-(1,4-bendioxan-2-yl-carbonyl) piperazine on a second generation α₁-acid glycoprotein column is described. Following optimisation of pH and organic modifier concentration using a modified simplex procedure, an optimum mobile phase composition of phosphate buffer (0.035 M) at pH 7.25 and acetonitrile (87:13 v/v) was established. The method was linear over the range 2.6 to 520 ng (on column) with relative standard deviations of 4.0 and 4.9% for the first and second eluting enantiomers, respectively. The limit of detection for the first and second eluting enantiomers, using UV detection at 254 nm, was 1.3 and 1.7 ng, respectively, on column.