The Research And Analysis Of The Quality Of The Preparation Of Oxidized Glutathione Inosine Compound Injection System

Liver fibrosis may further lead to cirrhosis and liver cancer.Researches showed that oxidized glutathione could apparently inhibit the occurrence and development of liver fibrosis,with the synergistic effect when using combined with inosine,it could use for the treatment of liver fibrosis secondary to various type of hepatitis.Purpose : This paper presents the investigation of synthetic route for oxidized glutathione and formulation of oxidized glutathione/inosine compound injection,the establishment of specifications for both drug substance and drug product.Also,the stability of oxidized glutathione/inosine compound injection has been studied.Method:Oxidized glutathione was synthesized by alkalization(Na OH),oxidization(H2O2),purification,freeze-dry and some other steps and effects of difference synthesis methods on yield and purity have been studied.Also,characterization was done by infrared and mass spectrum methods.Assays were established for oxidized glutathione and related substances using a HPLC method,quality of drug substance was controlled by parameters such as physic-chemical property,bacterial endotoxin,and microbial limit.Specification was established for drug substance and stability was investigated by stress?long term and accelerated tests.Formulation of oxidized glutathione/inosine compound injection was screened,optimized and determined by investigation of the effect that different p H exert to solution stability,as well as the impact to formulation from temperature,filter medium,nitrogen and so on.Assays were established for drug product and related substances using a HPLC method,quality of drug product was controlled by parameters such as physic-chemical property,bacterial endotoxin,and microbial limit.Specification was established for drug product and stability was investigated by stress?long term and accelerated tests.Results:Satisfactory results have been obtained for abovementioned studies.Firstly,an optimal synthetic route was determined,reduced glutathione as starting material was alkalified by Na OH and oxidized by H2O2,then subjected to ethanol precipitation,and3 batches of oxidized glutathione were synthesized,yield and purity are both acceptable.Secondly,formulation of oxidized glutathione/inosine compound injection was optimized and determined,this formulation was transferred to pilot-plant scale production and investigated.For QA aspect,oxidized glutathione and its compound injection were subjected to quality monitoring and specifications were established,results proved reliable.Stability tests for drug substance and drug product suggested that both are stable.Conclusion:Synthetic route for oxidized glutathione is reasonably feasible;Oxidized glutathione compound injection is quality-controllable with a satisfactory stability profile.Assays are highly sensitive and specific.Further investigations are warranted.