Study On Quality Standard Of Metronidazole Suppository

Objective:To promote the safety and accuracy of metronidazole suppository for clinical use,establish the quality standard of metronidazole suppository,and provide evidence and support for clinical drug use.Methods:The impurity spectrum of metronidazole was analyzed by impurity control method.The related substances in metronidazole suppositorywas validated by high performance liquid chromatography(HPLC)method.By the thermal circulation freeze-thaw experiment,the stability of metronidazole suppository was investigated in terms of traits,melting time limit,release amount,related substances and content;hydrochloric acid solution(9→1000),water,pH=4.0 acetate buffer and pH=6.8 phosphate buffer solution were used for dissolution medium,80-mesh,120-mesh,150-mesh,200-mesh raw material samples were tested for dissolution,and the effect of particle size on dissolution was investigated;liquid chromatography-mass spectrometry,diode array detector,and self-made metronidazole suppository and the original metronidazole suppository were mixed to be injected,compare the number of impurities and the impurity content of the two.Results:According to the 2013 edition of the British Pharmacopoeia,the impurity spectrum analysis of metronidazole suppository was carried out.The impurity A source was metronidazole synthesis intermediate of metronidazole synthesis,impurity E and impurity F were by-products of synthesis,and impurities B,C and D were the by-product produced in the reaction of the impurity imidazole in the raw material 2-methylimidazole during the metronidazole synthesis,the impurity G is the by-product of the oxidation of metronidazole;the content of the related substance in the metronidazole is investigated,and the 2-methyl-5-nitrate in the test solution is tested.The content of imidazole is less than 0.1%,the content of other single impurities is less than 0.1%;the sum of each impurity content is less than 0.2%,which meets the impurity limit requirement;the thermal cycle freeze-thaw test of 0 days,4 days,8 days,12 days,metronidazole suppository were all milky white suppositories.The suppositories were softened in 22-23 minutes.There was no hard heart during the pressing.There was no change in the release rate,related substances and contents,which proved that metronidazole suppository was stable.Different dissolution media were used to different particles.The metronidazole suppository was tested and its release curve was consistent,indicating that the particle size had no effect on the release of metronidazole suppository.Compare the self-made metronidazole suppository with the original metronidazole suppository,the spectrum and related substances,the number of impurities,impurity structure,all the impurity profile consistent.Conclusion:The quality standard of metronidazole suppository was established by investigating the impurity spectrum and related substance content of metronidazole suppository,which provided the basis for clinical drug use.