注射用头孢唑林钠溶液澄清度与细胞毒性相关性研究

摘要

ABSTRACT:OBJECTIVE To study the correlation between clarity of solution and cytotoxicity of cefazolin sodium for injection and evaluate the cytotoxicity test results of samples and rubber stopper from 2009 and 2011 by establis-hing the cytotoxicity test of cefazolin sodium for injection.METHODS Using L929 cells and MTT assay,the sample concentration was 0.78 mg・ mL-1 ,and use cefazolin sodium active pharmaceutical ingredient as negative control.The relative inhibition of proliferation was used as evaluation indicator,the turbidity values was used to characterize clarity of solution of samples.RESULTS There was a negative linear correlation between the sample turbidity value and the relative inhibitory effect of cell proliferation with the sample at a concentration of 0.78 mg・ mL-1 .Namely clarity of solution being worse,cytotoxicity may be bigger.When the sample turbidity was more pronounced than that of the reference suspensionⅣ,compared with cefazolin sodium active pharmaceutical ingredient,the cytotoxicity of the sam-ple was close to level 2.The toxic substance that has an impact on cell growth is not the cause of the decline in clarity of solution,but the clarity of solution test results for the samples that use non-coated halogenated butyl rubber stopper can be used as the reference index of cytotoxicity.CONCLUSION Based on the fact that butyl rubber stopper may increase the cytotoxicity of medicines,we recommend that the biosafety performance tests of the quality standard for pharmaceutical halogenated butyl rubber stopper should also include in cytotoxicity test,in addition to pyrogen,he-molysis,and acute toxicity test,to evaluate potential effects the rubber stopper migratory substances on cytotoxicity.%目的：通过建立注射用头孢唑林钠细胞毒性检测方法，评价2009年和2011年国抽部分样品及胶塞的细胞毒性，探讨注射用头孢唑林钠溶液澄清度与细胞毒性的相关性。方法采用L929细胞，MTT 比色法，以样品浓度0．78mg・ mL －1为评价浓度，以头孢唑林钠原料为阴性对照，以相对增殖抑制度为评价指标，以浊度值表征样品澄清度。结果样品浊度值与样品在浓度为0．78mg・ mL －1时的细胞相对增殖抑制度之间有负的直线相关关系；当样品浊度大于4号时，与头孢唑林钠原料相比，样品的细胞毒性已接近2级。对细胞生长产生影响的毒性物质不是造成澄清度下降的主要物质，但是样品澄清度越差则细胞毒性可能越大。结论药用卤化丁基胶塞质量标准中，除了热原、溶血和急性毒性试验，生物安全性能检查项目中还应包括细胞毒性试验。