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

A direct, isocratic, and simple chromatographic method is described for the resolution of racemic albuterol using the alpha(1)-acid glycoprotein chiral stationary phase (AGP-CSP) under reverse phase conditions. The effect of various organic modifiers, temperature, and phosphate buffer ionic strength on the separation factor (alpha) and stereochemical resolution factor (R(s)) has been studied. The enantiomeric separation of albuterol was also achieved using a urea-type CSP of (S)-indoline-2-carboxylic acid and (R)-1-(alpha-naphthyl)ethylamine, known as Chirex 3022, running in the normal phase mode. The effect of different organic acids added to the mobile phase was examined and the chiral recognition mechanism(s) is discussed. Solid phase extraction with C-18 Sep-Pak cartridges was applied as a clean-up step to determine the enantiomeric ratio between (-)-R and (+)-S-albuterol in pharmaceutical formulations and in human plasma. (C) 1995 Wiley-Liss, Inc.