Real-time Quantitative Monitoring of Synthesis Process of Clevidipine Butyrate Using Raman Spectroscopy

A direct synthesis process of clevidipine butyrate was used for testing the real-time detection performance of Raman spectroscopy in this study. The decrease of the reactant (Chloromethyl butyrate) and the increase of the product (Clevidipine butyrate) were used as indexes to evaluate the synthesis process using a 785-nm Raman spectrometer. Calibration models were built for the quantification of chloromethyl butyrate and clevidipine butyrate. The issue of linear regression distortions was overcome by setting solvent (acetonitrile) as internal standard. The validation results indicated that the Raman spectroscopy method was reproducible and accurate for monitoring the synthesis process. The real-time data were achieved to evaluate the esterification reaction of clevidipine butyrate under different conditions.