Quantification of enantiomers by mass spectrometry based on chemical derivatization and spectral shape deformation...

A facile mass spectrometric kinetic method for quantitative analysis of chiral compounds was developed by integrating mass spectrometry based on chemical derivatization and the spectral shape deformation quantitative theory. Chemical derivatization was employed to introduce diastereomeric environments to the chiral compounds of interest, resulting in different abundance distribution patterns of fragment ions of the derivatization products of enantiomers in mass spectrometry. The quantitative information of the chiral compounds of interest was extracted from complex mass spectral data by an advanced calibration model derived based on the spectral shape deformation quantitative theory. The performance of the proposed method was tested on the quantitative analysis of R-propranolol in propranolol tablets. Experimental results demonstrated that it could achieve accurate and precise concentration ratio predictions for R-propranolol with an average relative predictive error (ARPE) of about 4%, considerably better than the corresponding results of the mass spectrometric method based on chemical derivatization and the univariate ratiometric model (ARPE: about 12%). The limit of detection (LOD) and limit of quantification (LOQ) of the proposed method for the concentration ratio of R-propranolol were estimated to be 1.5% and 6.0%, respectively. The proposed method is complementary to the existing methods designed for the quantification of enantiomers such as the Cooks kinetic method.