凝胶法检查地舒单抗注射液细菌内毒素的可行性研究  

Study on feasibility of Gel-clot method for bacterial endotoxin test of denosumab injection

作　　者：王燕妮 蒋惠源 罗亦灵 杨宇 钮晓淑 WANG Yanni;JIANG Huiyuan;LUO Yiling;YANG Yu;NIU Xiaoshu(Taizhou Institute for Drug Control,Jiangsu Taizhou 225300,China)

机构地区：[1]泰州市药品检验院,江苏泰州225300

出　　处：《中国药品标准》2024年第6期590-595,共6页Drug Standards of China

基　　金：泰州市科技计划项目(No.SSF20230159)。

摘　　要：目的:探索凝胶法检查地舒单抗注射液细菌内毒素的可行性。方法:参照《中华人民共和国药典》2020年版三部通则1143和美国注射剂协会发布的《第82号技术报告:低内毒素回收率》,采用动态浊度法检测地舒单抗注射液细菌内毒素并考察其是否存在LER现象,以所得不同稀释度样品的内毒素回收率大小预测其对鲎试剂的干扰程度;再选用不同灵敏度的凝胶法鲎试剂进行干扰预实验;最后用不同厂家鲎试剂对三个不同批号的地舒单抗注射液分别进行凝胶法干扰试验。结果:地舒单抗注射液对细菌内毒素无掩蔽作用,但高浓度对鲎试剂与细菌内毒素的凝集反应有干扰作用。用BET用水稀释至浓度不大于6 mg·mL^(-1)时,即可认为对0.25 EU·mL^(-1)灵敏度及以上的凝胶法鲎试剂反应无干扰。结论:凝胶法检查地舒单抗注射液细菌内毒素的方法可行,可作为常规质量控制手段。Objective:To explore the feasibility of gel-clot method for bacterial endotoxin test of denosumab injection.Methods:Referring to general chapter 1143 in ChP 2020.VolⅢand Technical Report No.82 on Low Endotoxin Recovery published by PDA,bacterial endotoxin was detected by turbidimetric kinetic method and the endotoxin recovery of denosumab injection with different dilutions was calculated.Then based on the recovery,it was judged whether there was a LER issue and it was predicted how well the samples interfered the reaction between TAL reagent and bacterial endotoxin.Pre-experiment of gel-clot interference test was performed with TAL reagents of different sensitivity.The gel-clot interference test was performed for three batches of samples and the bacterial endotoxin was tested with TAL reagents from different manufacturers separately.Results:Denosumab injection had no LER issue,and whose high concentration had the interference on the reaction between TAL reagent and bacterial endotoxin.The interference of gel-clot TAL reagent having a sensitivity of not less than 0.25 EU·mL^(-1),was eliminated by diluting the samples to 6 mg·mL^(-1) with BET water.Conclusion:The gel-clot method for the detection of bacterial endotoxin in denosumab injection is feasible and can be used as a routine quality control method.

关 键 词：地舒单抗注射液 细菌内毒素 凝胶法 动态浊度法 低内毒素回收率 

分 类 号：R921.2[医药卫生—药学]