三种微球制剂的细菌内毒素质量控制方法研究  

Study on bacterial endotoxin detection method of three types of microsphere preparation

作　　者：裴宇盛 刘洋[3] 蔡彤 李清[1] PEI Yusheng;LIU Yang;CAI Tong;LI Qing(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;National Institute for Food and Drug Control,Beijing 102629,China;Jiangsu Institute for Food and Drug Control,Nanjing 210019,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]中国食品药品检定研究院,北京102629 [3]江苏省食品药品监督检验研究院,江苏南京210019

出　　处：《沈阳药科大学学报》2022年第11期1327-1332,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立注射用醋酸奥曲肽微球、注射用双羟萘酸帕瑞肽微球、艾塞那肽微球,三种肽类微球制剂的细菌内毒素检测方法。方法筛选微球的溶解剂将微球完全溶解释放其被包含的细菌内毒素,分别采用凝胶法、动态浊度法、动态显色法三种细菌内毒素检测方法进行干扰试验,研究三种方法能否排除有机溶剂和微球溶解物是否会对检测造成干扰,确定不干扰浓度并对三类微球制剂进行细菌内毒素检测。结果采用二甲基亚砜可将三类微球完全溶解,三种微球制剂的各三批样品采用凝胶法、动态显色法、动态浊度法的所有回收率结果均在50%~200%内,符合干扰试验要求,细菌内毒素检测结果均符合规定。结论注射用醋酸奥曲肽微球、注射用双羟萘酸帕瑞肽微球、艾塞那肽微球三种肽类微球制剂均可以采用二甲基亚砜进行溶解再进行细菌内毒素检查,三种细菌内毒素检查方法(凝胶法、动态浊度法、动态显色法)均可用于上述三种微球的细菌内毒素的质量控制。Objective To establish a bacterial endotoxin detection method for three peptide microsphere preparations including octreotide acetate microspheres for injection,pasireotide microspheres for injection,and exenatide microspheres.Methods Screen the dissolving agent of the microspheres to completely dissolve the microspheres to release the bacterial endotoxins contained therein,and then use the interference test of three bacterial endotoxin detection methods(gel-clot assay,kinetic-turbidimetric assay,kinetic-chromogenic assay)to study Whether organic solvents and dissolved microspheres interfere with the three types of endotoxin detection methods,determine the non-interference concentration and perform bacterial endotoxin testing for the three types of microsphere preparations.Results The three types of microspheres can be completely dissolved using dimethyl sulfoxide.The recovery results of the three batches of samples of the three microsphere preparations by the gel-clot assay,kinetic-turbidimetric assay,kinetic-chromogenic assay meet the requirements of the interference test,and the recovery value is in the range of 50%-200%.The test results of 9 batches of bacterial endotoxin all met the requirements.Conclusion Octreotide acetate microspheres for injection,Pasireotide pamoate microspheres for injection,and Exenatide microspheres can all be dissolved in dimethyl sulfoxide and then tested for bacterial endotoxin.,The three types of bacterial endotoxin inspection methods(gel-clot assay,kinetic-turbidimetric assay,kinetic-chromogenic assay)can be used for the quality control of bacterial endotoxin of the above microspheres.

关 键 词：醋酸奥曲肽 双羟萘酸帕瑞肽 艾塞那肽微球 细菌内毒素检查 凝胶法 动态浊度法 动态显色法 干扰试验 

分 类 号：R917[医药卫生—药物分析学]