Sudies On The Related Substance And Quality Control Of Bicyclol

Bicyclol is an anti-hepatitis drug developed by China.It has advantages of definite efficacy and high bioavailability,and was used for the treatment of alcohol-induced liver damage,nonalcoholic fatty liver disease,viral hepatitis,and brain injury.However,adverse reactions are observed during the clinical use of this drug,which were believed to be avoided by the quality control of the starting material and the related preparation.In the present work,quality control of both the starting material and the intermediate were studied,as well as the related substances in the product.Results of the study may provide suggestions for the production process optimization and quality improvement of bicyclol.In the first part,an HPLC method was developed and validated for the determination of raw material and major intermediates of bicyclol.All threemethods were established with good accuracy,precision,reproducibility,recovery,and linear relationship in predetermined range.They can be used for the content determination of raw material and major intermediates of bicyclol.In the second part,Box-Benhnken Design(BBD)was employed for the optimization of the HPLC method for the separation of bicyclol and its major intermediate.The result indicated that baseline separation was achieved for bicyclol and the major intermediates within 40 min under the condition as followes: column temperature 30 ?C,mobile phase pH 4.20,flow rate 1.2 mL/min.In the third part,column chromatography was used for the isolation of the related substance in bicyclol preparation,and furnished one compound which was identified to be bifendate by NMR and MS spectrometry.It was proposed that bifendate originated from the raw materials used in the production of bicyclol.