Determination of the enantiomeric composition of some molecules of pharmaceutical interest by chemometric analysis of the UV spectra of cyclodextrin guest–host complexes

In the present study, chemometric analysis of UV spectral data of cyclodextrin guest–host complexes was used to develop multivariate regression models that were subsequently used to determine the enantiomeric composition of samples of ibuprofen and norephedrine. Partial-least-squares regression models (PLS-1) were made for both compounds with (alpha)-, (beta)-, (gamma)-cyclodextrins (CDs). Using a regression model with five PLS components, the quadratic mean of the percent relative error (QM% RE) in the mol fraction of (S)-(+)-ibuprofen obtained with independently-prepared test sets for the three cyclodextrins was: 2.7% ((alpha)-cyclodextrin), 0.8% ((beta)cyclodextrin), and 0.7% ((gamma)-cyclodextrin). Similar studies conducted with norephedrine using a regression model with five PLS components gave QM%RE-values in the mol fraction of (1S, 2R)-norephedrine of: 5.9% ((alpha)-cyclodextrin), 3.4% ((beta)-cyclodextrin), and 3.3% ((gamma)-cyclodextrin). The results are discussed in terms of compatibility in guest–host molecular sizes, binding strength, and the three-point interaction model for enantiomeric separation.