Simultaneous rapid structure identification and accurate quantitation of chiral drugs based on home-built polarized Raman microscope

Chiral drug with different enantiomers exhibits different pharmacological activities. Structure identification, quality control, and accurate quantitation are all important issues for chiral drug. So far, these concerns can only be studied by different techniques solely, one method which can investigate the all-abovementioned issues simultaneously is needed, such approach can definitely promote the development of drug industry. Raman spectroscopy has long been used for quantitation and also utilized for chirality study in recent years, thanks to its molecular fingerprints and the optical activity of chiral molecule. In this study, we firstly investigate the polarization sensitivity of racemic ibuprofen and its (S)-enantiomer using our home-built polarized Raman microscope, then successfully distinguish the racemic and its (S)-enantiomer by Raman optical activity (ROA) spectra and its principal component analysis (PCA) scatter plot. Notably, the combination of polarized Raman spectroscopy and partial least squares regression (PLSR) is proposed to achieve accurate quantitation of commercial ibuprofens. The experimental results of a coefficients of determination (R²) are 0.957 for racemic ibuprofen and 0.988 for (S)-ibuprofen, and their root mean square error of prediction (RMSEP) values are 0.126% and 0.049% respectively. These premilitary results give hint that polarized Raman spectroscopy (PRS) is a powerful non-destructive analytical tool for drug applications.