Chiral purity test of metoprolol enantiomer after derivatization with (-)-menthyl chloroformate by reversed-phase high performance liquid chromatography

Arch Pharm Res. 1999 Dec;22(6):614-8. doi: 10.1007/BF02975334.

Abstract

A reversed-phase high-performance liquid chromatographic method was developed to determine the optical purity of metoprolol enantiomers. The enantiomers were converted to diastereomeric derivatives using (-)-menthyl chloroformate reagent. Separation of the enantiomers as diastereomers was achieved by reversed-phase HPLC within 30 min using Inertsil C8 column. This method allowed determination of 0.05% of either enantiomer in the presence of its stereoisomer and method validation showed adequate linearity over the required range. Owing to the reaction condition during the derivatization with (-)-menthyl chloroformate, the possibility of racemization had to be established. Different ratios of (S)-(-)-metoprolol and (R)-(+)-metoprolol were prepared. Enantiomeric separation of these mixtures took place on a chiralcel OD column or, after derivatization with (-)-menthyl chloroformate, on a C8 column. The results from the these two independent separation systems were compared with trace racemization and were in very good agreement. No racemization was found during the experiment.

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Formates / chemistry*
  • Metoprolol / chemistry*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Stereoisomerism

Substances

  • Formates
  • menthyl chloroformate
  • Metoprolol