Method for resolving metoprolol enantiomers by using simulated moving bed chromatography

Abstract

The invention discloses a method for resolving metoprolol enantiomers by using simulated moving bed chromatography. The method is characterized in that the simulated moving bed chromatography is adopted, an amylose-tris(3,5-dimethylphenylcarbamate) is used as a filler and n-hexane and an alcohol organic modifier are used as a mobile phase, to resolve the metoprolol enantiomers under a positive phase condition, thus obtaining high-pure R-metoprolol and S-metoprolol. The simulated moving bed chromatography is continuous production, has high automatic degree and high production efficiency.

Description

technical field [0001] The invention relates to a separation technology of chiral drugs, in particular to a simulated moving bed chromatographic separation method of metoprolol. Background technique Metoprolol is a selective β1 receptor blocker, which is widely used clinically in the treatment of cardiovascular diseases. Metoprolol is an optically active compound with a pair of enantiomers, and it is currently administered in the form of a racemate clinically. Studies have shown that the receptor affinity of the S-enantiomer is 25 times that of its R-enantiomer. In isolated hearts, its S-enantiomer blocked isoproterenol-activated adenylate cyclase activity 33-fold more than its enantiomer. There is also stereoselectivity in the metabolic process, and the first-pass effect of its S-enantiomer is lower. Due to the significant differences in pharmacodynamics and pharmacokinetics of the two enantiomers, enantiomer separation is of great significance for further research on ...

AI Technical Summary

Problems solved by technology

In recent years, simulated moving bed chromatography technology has achieved rapid development in the separation of drugs, but there is still no public report on the separation of metoprolol enantiomers using simulated moving bed chromatography