量反应平行线测定法在人凝血因子Ⅷ效价测定中的应用  

Establishment of Statistical Analysis Method for Biological Activity Determination of Human Coagulation Factor Ⅷ

作　　者：史卓维[1] 王鸣人 段徐华[1,2] 邵泓 陈钢[1] SHI Zhuo-wei;WANG Ming-ren;DUAN Xu-hua;SHAO Hong;CHEN Gang(NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai Institute for Food and Drug Control,Shanghai 201203,China;Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China)

机构地区：[1]上海市食品药品检验所,国家药品监督管理局治疗类单抗质量控制重点实验室,上海201203 [2]复旦大学生物医学研究院,上海200032

出　　处：《中国药学杂志》2022年第7期573-577,共5页Chinese Pharmaceutical Journal

摘　　要：目的建立适用于人凝血因子Ⅷ效价测定(一期法)的统计分析方法。方法采用一期法对人凝血因子Ⅷ的效价进行测定,采用量反应平行线测定法进行效价计算,并对该方法进行方法学验证。采用经验证的方法对来自7家企业的21批人凝血因子Ⅷ样品进行效价测定,并与标准曲线带入法进行比较。结果效价测定范围为标示量的64%~156%;以效价测定值的对数对理论值的对数作线性回归,相关系数r为0.9904;相对偏倚为0.5%~3.1%,其90%置信区间为-3.8%~6.1%;中间精密度为3.8%~6.7%,其95%置信上限为7.0%~12.3%;不同批次的激活的部分凝血活酶(APTT)试剂和人凝血因子Ⅷ缺乏血浆,对测定结果的影响无统计学意义,方法耐用性良好。采用量反应平行线测定法对21批样品进行测定,其结果与标准曲线带入法的结果表现出良好一致性。结论与标准曲线带入法相比,应用量反应平行线测定法分析一期法测定的人凝血因子Ⅷ效价,可增加实验数据的可靠性,并有效控制测定方法的误差,从而更好地控制人凝血因子Ⅷ质量。OBJECTIVE To establish a statistical analysis method for biological activity determination of human coagulation factorⅧ(one-stage assay).METHODS The biological activity of human coagulation factorⅧwas determined by one-stage assay,the results were calculated by parallel-line model,and then the method was verified.Finally,21 batches of human coagulation factorⅧfrom seven manufacturers were investigated using the method and the results were compared with those calculated by standard curve method.RESULTS The determination range was between 80%and 140%of the potency stated on the label,the correlation coefficients between measured and labelled values was 0.9904.The relative bias ranged from 0.5%to 3.1%,with 90%confidence intervals from-3.8%to 6.1%.The intermediate precision was 3.8%-6.7%,with 95%upper confidence limit from 7.0%-12.3%.The effects of APTT and human coagulation factorⅧdeficiency plasma on the determination results were not statistically significant,and the method showed good robustness.The results of 21 batches measured by parallel-line model were in good agreement with those obtained by standard curve method.CONCLUSION Compared with the standard curve method,the analysis of the biological activity determined by one-stage assay with parallel-line model can increase the reliability of the data and effectively control the error of the determination method,so as to control the quality of human coagulation factorⅧbetter.

关 键 词：人凝血因子Ⅷ 效价测定 一期法 量反应平行线测定法 

分 类 号：R917[医药卫生—药物分析学]