基于Zeta电位表征血小板因子4/依诺肝素钠复合物的方法学研究  

Development of a Zeta potential method to characterize platelet factor 4-enoxaparin complex

作　　者：赵婧雯 欧阳艺兰 钱玉兰[2] 刘志 易琳 张真庆[1] ZHAO Jing-wen;OU-YANG Yi-lan;QIAN Yu-lan;LIU Zhi;YI Lin;ZHANG Zhen-qing(College of Pharmaceutical Sciences,Soochow University,Suzhou Jiangsu 215006;The First Affiliated Hospital of Soochow University,Suzhou Jiangsu 215129;Suzhou Erye Pharmaceutical Co.,Ltd,Suzhou Jiangsu 215002)

机构地区：[1]苏州大学药学院,江苏苏州215006 [2]苏州大学附属第一医院,江苏苏州215129 [3]苏州二叶制药有限公司,江苏苏州215002

出　　处：《中南药学》2023年第10期2666-2671,共6页Central South Pharmacy

基　　金：江苏省研究生科研与实践创新计划项目(No.SJCX21_1357)。

摘　　要：目的建立Zeta电位法研究血小板因子4/依诺肝素钠(PF4/Eno)复合物表面电荷的方法,以比较和评价肝素类样品潜在的免疫原性。方法考察不同孵育时间、不同PF4/Eno摩尔比例对PF4/Eno复合物表面电荷的影响,并对方法的精密度和专属性进行分析验证。结果孵育时间在10~30 min时PF4/Eno复合物较为稳定;PF4/Eno复合物的PHR_(ζ=0)值约为12,PF4/Hp复合物的PHR_(ζ=0)值约为48,差异有统计学意义(P<0.001),表明方法具有较好的专属性;日内精密度RSD<8.0%,日间精密度RSD为8.2%,表明方法精密度良好。结论建立的方法可以用于比较和评价肝素类样品潜在的免疫原性,并为依诺肝素钠仿制药的免疫原性一致性评价提供理论和方法上的参考。Objective To develop a Zeta potential method to characterize the surface charge of platelet factor 4/enoxaparin(PF4/Eno)sodium complex,and to compare and evaluate the potential immunogenicity of heparin samples.Methods The effect of different incubation time and PF4/Eno molar ratios on the surface charge of PF4/Eno sodium complex was determined.The precision and specificity of the method were verified.Results The PF4/Eno was relatively stable within 10~30 min of incubation.The PHR_(ζ=0) of PF4/Eno complex was about 12,and the PHR_(ζ=0) of PF4/Hp complex was about 48,with a significant difference(P<0.001),indicating good specificity of the method.The within-day precision RSD was less than 8.0%,and the inter-day precision RSD was 8.2%,demonstrating proper precision of the method.Conclusion This method can be used to compare and evaluate the potential immunogenicity of heparin samples,and provide a theoretical and a methodological reference for the consistent evaluation of immunogenicity of enoxaparin sodium generics.

关 键 词：肝素诱导的血小板减少症 血小板因子4 依诺肝素钠 Zeta电位法 

分 类 号：R917[医药卫生—药物分析学] R94[医药卫生—药学]