Chiral separations of β-blocking drug substances using the Pirkle-type α-Burke 1 chiral stationary phase

Abstract

The Pirkle-type α-Burke 1 chiral stationary phase (CSP) column has been evaluated for the enantiomeric separation of β-blocking drug substances and suitability for the determination of enantiomeric purity of these substances. Eighteen β-blockers currently on sale in Denmark were investigated. By varying the amount of alcohol modifier in the mobile phase, a total of fifteen of the eighteen investigated β-blockers were successfully separated by straight-phase HPLC within acceptable analysis times (i.e. below 20 min). The separation factors ranged between 1.07 and 1.41, and the resolutions were in no case less than 0.9. The possible use of the column for a direct determination of enantiomeric purity of the drug substances was also investigated. Validation studies, in which the enantiomers of propranolol were used, were performed in accordance with the ICH guideline, Validation of Analytical Procedures. The limit of detection for R-propranolol in S-propranolol was estimated to be ca. 0.1% and the limit of quantification ca. 0.3%.