Applied Circular Dichroism: A Facile Spectroscopic Tool for Configurational Assignment and Determination of Enantiopurity

Abstract

In order to determine if electronic circular dichroism (ECD) is a good tool for the qualitative evaluation of absolute configuration and enantiopurity in the absence of chiral high performance liquid chromatography (HPLC), ECD studies were performed on several prescriptions and over-the-counter drugs. Cotton effects (CE) were observed for both S and R isomers between 200 and 300 nm. For the drugs examined in this study, the S isomers showed a negative CE, while the R isomers displayed a positive CE. The ECD spectra of both enantiomers were nearly mirror images, with the amplitude proportional to the enantiopurity. Plotting the differential extinction coefficient (Δε) versus enantiopurity at the wavelength of maximum amplitude yielded linear standard curves with coefficients of determination (R2) greater than 97% for both isomers in all cases. As expected, Equate, Advil, and Motrin, each containing a racemic mixture of ibuprofen, yielded no chiroptical signal. ECD spectra of Suphedrine and Sudafed revealed that each of them is rich in 1S,2S-pseudoephedrine, while the analysis of Equate vapor inhaler is rich in R-methamphetamine.