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. (C) 2004 Elsevier B.V. All rights reserved.