Structure elucidation and limit setting of unknown impurity of dihydrostreptomycin
In order to scientifically establish the limit standard of unknown impurity in dihydrostreptomycin products,the study was conducted from three aspects:molecular structure,source and quality stability.Firstly,preparative chromatography was used to prepare pure impurity from dihydrostreptomycin,and LC-HRMS and NMR techniques were used for chromatographic analysis to study the molecular structure of impurities.Secondly,the impurity source was investigated by HPLC method combined with the dihydrostreptomycin production process.Finally,experiments of various influencing factors were designed to verify the quality stability of the impurity.The results show that the molecular structure of the impurity was similar to that of dihydrostreptomycin and belonged to aminoglycoside.The impurity was derived from the streptomycin analogue produced in the fermentation stage of dihydrostreptomycin,which becomes the unknown impurity of dihydrostreptomycin product through hydrogenation reduction.The impurity is not sensitive to acid,alkali,high temperature,oxidation,light and other factors,and has good stability.The related impurity produced by streptomycin fermentation metabolism has good stability,and it is safe and reasonable to set the limit standard that the peak area fraction is less than or equal to 1.0%,which provides important reference value for clinical medication.
chromatography analysisdihydrostreptomycinstructure elucidationlimit of impurityclinical medication
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