DIRECT SEPARATION OF ALBUTEROL ENANTIOMERS IN BIOLOGICAL-FLUIDS AND PHARMACEUTICAL FORMULATIONS USING ALPHA(1)-ACID GLYCOPROTEIN AND PIRKLEUREA TYPE COLUMNS

A direct, isocratic, and simple chromatographic method is described fo r the resolution of racemic albuterol using the alpha(1)-acid glycopro tein chiral stationary phase (AGP-CSP) under reverse phase conditions. The effect of various organic modifiers, temperature, and phosphate b uffer ionic strength on the separation factor (alpha) and stereochemic al resolution factor (R(s)) has been studied. The enantiomeric separat ion of albuterol was also achieved using a urea-type CSP of (S)-indoli ne-2-carboxylic acid and (R)-1-(alpha-naphthyl)ethylamine, known as Ch irex 3022, running in the normal phase mode. The effect of different o rganic acids added to the mobile phase was examined and the chiral rec ognition mechanism(s) is discussed. Solid phase extraction with C-18 S ep-Pak cartridges was applied as a clean-up step to determine the enan tiomeric ratio between (-)-R and (+)-S-albuterol in pharmaceutical for mulations and in human plasma. (C) 1995 Wiley-Liss, Inc.