Analytical determination of enantiomeric purity using Raman optical activity

Increased restrictions on the enantiomeric purity of pharmaceuticals underscore the need for improved analytical techniques to quantitate chiral purity. The method of scattered circularly polarized Raman optical activity (SCP ROA) is examined as a potentially useful analytical technique. Preliminary studies revealed SCP ROA measurements were reproducible to within current experimental noise limits and displayed the expected linear decrease in SCP ROA with increasing racemization of the enantiomeric mixtures. Minimal interference in SCP ROA signal was observed when either an achiral or another chiral entity was present in a mixture. The advantages of spectral subtraction techniques were demonstrated for separation of SCP ROA signals when multiple chiral entities are present. SCP ROA has been shown to be capable of quantitative analysis and is capable of simultaneous identification of multiple enantiomeric species. This is significant since traditional optical activity measurements, such as polarimetry and circular dichroism, are of limited value on mixtures where the impurities are not quantitatively defined.