| Levofloxacin(LVFX)is a total synthetic antibiotic with broad-spectrum,its doses have broad applications in clinic treatment.To improve the quality of LVFX,protect the drug safety and eliminate drug misadventures fundamentally,research and controlling study of unknown impurity G in LVFX which synthesized by our research team were conducted.An unknown impurity which was greater than 0.10% was found in LVFX sample,according to the test method of related substance in Chinese Pharmacopeia of version 2010.Impurity was isolated by flash column chromatography and prepatative high performance liquid chromatography.This impurity which was greater than 0.10% was identified to be Levofloxacin ethyl ester,on the basis of IR,UV,LCMS and NMR spectra of isolated impurity sample and the comparison with literature data and spectra of known substance.Research on mechanism showed that the impurity formed in the side reaction at recrystallization step of crude LVFX.According to the analytical result of organic impurity,study on single factor analysis of impurity content in recrystallization step and further orthogonel test analysis was conducted.Controlling of impurity content was achieved by optimized parameters of recrystallization.The content of the major impurity(Levofloxacin ethyl ester)in LVFX was lower than 0.01% and the quality of LVFX was greatly improved.The total yield of LVFX was 45.2%. |
