单磷酰脂A佐剂的热原控制方法研究  

Study on quality control method for pyrogen of monophosphoryl lipid A adjuvant

作　　者：裴宇盛 蔡彤 陈晨 高华 PEI Yu-sheng;CAI Tong;CHEN Chen;GAO Hua(Division of Pharmacology,Institute for Chemical Drug Control,National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院化学药品检定所药理室,北京102629

出　　处：《中国药理学通报》2020年第8期1174-1177,共4页Chinese Pharmacological Bulletin

基　　金：国家科技部“重大新药创制”科技重大专项(No 2018ZX09101001-003-005)。

摘　　要：目的研究建立单磷酰脂A佐剂的热原控制方法。方法对2批不同来源的单磷酰脂A分别采用细菌内毒素检查法、TLR2高表达HEK细胞和TLR4高表达HEK细胞报告基因法进行了线性与范围、专属性、检测限、耐用度、回收率等方法学研究。结果2批样品使用3种方法的线性与范围、检测限、耐用度、回收率等方法学研究结果均符合规定。专属性方面的研究显示,细菌内毒素检查法、TLR4高表达HEK细胞报告基因法不能区分细菌内毒素和单磷酰脂A。结论细菌内毒素检查法、TLR4高表达HEK细胞报告基因法检测专属性均无法满足质量控制要求。TLR2高表达HEK细胞报告基因法可作为单磷酰脂A佐剂的热原控制方法。Aim To establish a pyrogen control method for monophosphoryl lipid A adjuvant.Methods Two batches of different sources of monophosphoryl lipid A were tested by bacterial endotoxin test,and TLR2/TLR4 high expression HEK cell reporter gene method was used for linearization.Methodological studies were carried out on scope,specificity,detection limits,durability,and recovery.Results The methodological results of the three methods of two batches of samples were consistent with the requirements of linearity and range,detection limit,durability and recovery.Specificity studies showed that bacterial endotoxin test,TLR4 high expression of HEK cell reporter gene method could not distinguish between bacterial endotoxin and MPLA.Conclusions Bacterial endotoxin test and TLR4 high expression HEK cell reporter gene assay specificity can not meet the quality control requirements.The TLR2 high expression HEK cell reporter gene method can be used as a pyrogen control method for the monophosphoryl lipid A adjuvant.

关 键 词：单磷酰脂A 佐剂 细菌内毒素检查法 报告基因法 热原检查 质量控制 

分 类 号：R363.14[医药卫生—病理学] R392.11[医药卫生—基础医学]