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目的体内生物学活性是重组人促红细胞生成素(Recombinant human erythropoietin,rhuEPO)质量控制的关键指标之一,通过研究找出实验小鼠数量对rhuEPO体内活性测定结果的影响,减少检测的复试率和误判率,控制质量风险。方法根据《中国药典》三部的方法,按低、中、高3个剂量组,分别于皮下注射人促红细胞生成素(EPO)标准品和样品溶液,在注射后第4天从小鼠眼眶后静脉丛采血测定EPO活性。根据实验设计每剂量组实验小鼠分别选择为3只、4只、6只、9只、12只,通过实验观察每剂量组小鼠数量不同对rhuEPO内活性测定结果的影响。结果每剂量组小鼠为3只的EPO活性测定复试率、相对标准偏差、最大误差范围和误判率都远高于小鼠数为4—12只各组的EPO活性测定结果;每剂量组小鼠只数为4只和6只的实验复试率、相对标准偏差和最大误差范围相差不大;每剂量组小鼠为9只和12只的实验复试率、相对标准偏差、最大误差范围和误判率均低于其他3个实验。结论每剂量组小鼠数量越多,EPO活性测定的相对标准偏差、误差范围和误判率等越低,结合检测成本及实际可操作性,我们认为每剂量组小鼠数量设为9只为EPO生物学活性测定最佳的小鼠使用数量。
Objective The biological activity in vivo is one of the key indicators for the quality control of recombinant human erythropoietin (rhuEPO). The effects of the number of experimental mice on the determination of rhuEPO activity in vivo are found out, and the retesting rate and False judgment rate, control quality risk. Methods According to the three methods of “Chinese Pharmacopoeia”, the human erythropoietin (EPO) standard and the sample solution were injected subcutaneously in low, medium and high dose groups respectively. On the 4th day after injection, Venous plexus blood was collected for EPO activity. According to the experimental design, the mice in each dose group were selected as 3, 4, 6, 9 and 12 mice, respectively. The effects of different numbers of mice in each dose group on the activity of rhuEPO were observed experimentally. Results The retesting rate of three EPO activities per dose group was significantly higher than that of the control group (P <0.05). The relative standard deviation, the maximum error range and the false positive rate were all significantly higher than those of 4-12 mice in each dose group. The experimental retest rate of mice with only 4 and 6 mice showed no significant difference between the relative standard deviation and the maximum error range. The experimental retest rate, relative standard deviation and maximum error range of 9 and 12 mice per dose group The false positive rate was lower than the other three experiments. Conclusion The greater the number of mice in each dose group, the lower the relative standard deviation, error range and false positive rate of EPO activity determination. Combined with the detection cost and practical operability, we consider the number of mice per dose group as 9 The optimal amount of mouse EPO used to determine the biological activity of EPO.