The Research Program Of Linezolid Injection And Rubber Plug Compatibility

Linezolid is a key project of Broadwell Pharmaceutical Co.,Ltd.in Jilin Province.The raw material drugs and preparations are all studied in imitation.The project is in the declaration stage.According to the national regulations,it is necessary to carry out the "Compatibility study of drugs and packaging materials".This paper focuses on the compatibility of linezolid injection and bromobutyl rubber plugs.The content is described in four parts:extraction,migration,adsorption and methodological verification.The sample of compatibility(inverted)placed in storage chambers under the required conditions.The method of high performance liquid chromatography(HPLC)for detecting antioxidant was verified.The method of gas chromatography mass spectrometry for detecting antioxidant and polycyclic aromatic hydrocarbons was verified in this paper.The result showed that the above method had good specificity,high sensitivity,good linearity,accurate results,good reproducibility,and it is suitable for all substances detection.The extraction experiment would examine the effects of different extraction and different extraction methods on additives in rubber stoppers,which was the basis for the subsequent migration experiment.Result:the antioxidants were not detected in the four extraction solutions.The nitrosamines and polycyclic aromatic hydrocarbons(PAHs)were detected in the methanol extraction solution.PAHs were detected in the linezolid injection and blank accessories solution.The nitrosamines and PAHs were not detected when water for injection was used as the extraction solution.In the migration test,the content of antioxidants,nitrosamines and PAHs in the linezolid injection was tested in 6-month accelerated test and 9-month long-term test.Results:Both hydrazine and phenanthrene were detected in the injection.The content of hydrazine and phenanthrene were below the limit of 2.5 ng/mL.The antioxidants and nitrosamines were not detected in the injection.It was proved that the migration amount of antioxidants,nitrosamines and PAHs in rubber plugs met the requirements in the linezolid injection.The adsorption test and injection stability were carried out simultaneously.The paper examined the changes of Linezolid injection content,related substances,traits,pH,the clarity of the solution,the insoluble particles and the characteristics of the rubber plug in high temperature,freeze-thaw cycles,light,6-month accelerated test and 9-month long-term test.The results showed that it was no change in the indicators of linezolid injection.The contents of lineazolamide were in the range of 95.0%～1 10.0%,linezolid related substances(impurities A,B,C,D,E,F,G,H)were all within the limits.It was proved that the rubber stopper had no adsorption effect on linezolid injection.The results showed that linezolid injection and bromobutyl rubber plug had good compatibility by extraction experiment,migration experiment and adsorption experiment.