第二批人血白蛋白国家对照品的研制标定  

Preparation of the Second Batch of National Standard for Human Albumin

作　　者：王敏力[1] 王箐舟[1] 吴利红 梁蔚阳[3] 李炎 余进 马力 陈家啡 丁亚凌 曹大伟 何永兵 张宝献 王弢 徐苗[1] 侯继锋[1] WANG Min-li;WANG Jing-zhou;WU Li-hong;LIANG Wei-yang;Li Yan;YU Jin;MA Li;CHEN Jia-fei;DING Ya-ling;CAO Da-Wei;HE Yong-bing;ZHANG Bao-xian;WANG Tao;XU Miao;HOU Ji-feng(National Institutes for Food and Drug Control,WHO Collaboration Center for Standardization and Evaluation of Biologicals,Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products,NMPA Key Laboratory for Quality Research and Evaluation of Biological Products,Beijing 100050,China;Shanghai Institute for Food and Drug Control,Shanghai 201203,China;Guangdong Institute for Drug Control,Guangzhou 510180,China;Sichuan Institute for Food and Drug Control,Chengdu 611731,China;Shanghai RAAS blood products Co.,Ltd.,Shanghai 200245,China;Hualan Biological Engineering,Inc.,Xinxiang 453003,China;Boya Bio-pharmaceutical Group Co.,Ltd.,Fuzhou 344000,China;Chengdu Rongsheng Pharmaceuticals Co.,Ltd.,Chengdu 610041,China;China Biologic Products Holdings,Inc.Taian 271000,China;Sichuan Yuanda Shuyang Pharmaceutical Co.,Ltd.,Chengdu 610214,China;Hualan Biological Engineering Chongqing Co.,Ltd.,404100,China;Lanzhou Institute of Biological Product Co.,Ltd.,Lanzhou 730046,China)

机构地区：[1]中国食品药品检定研究院,WHO生物制品标准化和评价合作中心,卫生部生物技术产品检定方法及标准化重点实验室,国家药品监督管理局生物制品质量研究与评价重点实验室,北京100050 [2]上海市食品药品检验研究院,上海201203 [3]广东省药品检验所,广州510180 [4]四川省食品药品检验检测院,成都611731 [5]上海莱士血液制品股份有限公司,上海200245 [6]华兰生物工程股份有限公司,河南新乡453003 [7]博雅生物集团股份有限公司,江西抚州344000 [8]成都蓉生药业有限责任公司,成都610041 [9]山东泰邦生物制品有限公司,山东泰安271000 [10]四川远大蜀阳药业有限责任公司,成都610214 [11]华兰生物工程重庆有限公司,重庆404100 [12]兰州生物制品研究所有限责任公司,兰州730046

出　　处：《中国药学杂志》2022年第24期2051-2060,共10页Chinese Pharmaceutical Journal

基　　金：重大新药创制课题“创新生物技术药评价及标准化关键技术研究”项目资助(2018ZX09101001);重大新药创制课题“重组人血白蛋白生产工艺、质量控制和临床研究(重组人血白蛋白质量控制关键技术和标准研究)”项目资助(2018ZX09301004)。

摘　　要：目的研制第二批人血白蛋白国家对照品,用于人血白蛋白等相关产品的质量活动。方法选择批签发检验合格的人血白蛋白产品作为原料进行合并、除菌、分装。制备后按照2020年版《中国药典》三部人血白蛋白各论要求,选择蛋白质含量、辛酸钠含量、乙酰色氨酸含量、多聚体含量、钠离子含量、pH、吸光度共7个检验项目进行多实验室协作标定。除乙酰色氨酸由5家实验室协作标定外,其余项目均由11家实验室完成协作标定。在LAB01开展对照品的稳定性监测。结果依据各实验室协作标定结果,该批国家对照品确立的参考范围分别为:蛋白质含量均值204.03 g·L^(-1),95%可信区间(203.05,205.00)g·L^(-1),参考范围(204.03±2.90)g·L^(-1);辛酸钠含量均值16.21 mmol·L^(-1),95%可信区间(15.98,16.44)mmol·L^(-1),参考范围(16.21±0.70)mmol·L^(-1);乙酰色氨酸含量均值16.28 mmol·L^(-1),95%可信区间(15.82,16.74)mmol·L^(-1),参考范围(16.28±0.74)mmol·L^(-1);多聚体峰面积百分比均值7.43%,95%可信区间(7.30,7.56)%,参考范围(7.43±0.38)%(HPLC-SEC);pH值均值6.95,95%可信区间(6.92,6.98),参考范围(6.95±0.08)[测定温度(22±5)℃];吸光度均值0.06,95%可信区间(0.06,0.06),参考范围(0.06±0.01);钠离子含量均值135.2 mmol·L^(-1),95%可信区间(131.2,139.2)mmol·L^(-1),参考范围(135±12)mmol·L^(-1)。所有检测项目结果在考察期内量值没有发生趋势性变化。结论该批人血白蛋白国家对照品符合相关要求,可以发放使用。OBJECTIVE To prepare the second batch of Chinese national standard for human albumin used for the test of batch release or other quality control of human albumin products.METHODS The national standard for human albumin was prepared with batch released human albumin products,mixed and filled under aseptic conditions.Cooperative calibration according to the unified methods recorded in China Pharmacopeia 2020 was carried out in collaboration laboratories and seven test items including total protein content,sodium caprylate,acetyltryptophan,polymers content,pH,absorbance,sodium content were detected.Except that the content of acetyl tryptophanate was calibrated by five laboratories,other calibration projects were completed by 11 laboratories.Monitoring of the stability of the national standard was carried out in LAB01.RESULTS The limits of the seven test items were established as follows after collaboration data was received and statistically analyzed:total protein mean content 204.03 g·L^(-1),95%CI of mean(203.05,205.00)g·L^(-1),control range(204.03±2.90)g·L^(-1);sodium caprylate mean content 16.21 mmol·L^(-1),95%CI of mean(15.98,16.44),control range(16.21±0.70)mmol·L^(-1);acetyl tryptophanate mean content 16.28 mmol·L^(-1),95%CI of mean(15.82,16.74),control range(16.28±0.74)mmol·L^(-1);polymers peak area mean 7.43%,95%CI of mean(7.30,7.56)g·L^(-1),control range(7.43±0.38)%(HPLC-SEC);pH mean 6.95,95%CI of mean(6.92,6.98),control range(6.95±0.08)[T(22±5)℃];absorbance mean 0.06,95%CI of mean(0.06,0.06),control range(0.06±0.01);sodium content mean 135.2 mmol·L^(-1),95%CI of mean(131.2,139.2),control range(135±12)mmol·L^(-1).CONCLUSION The prepared national standard for human albumin met the relevant requirements and may be served as national standard for human albumin products.

关 键 词：人血白蛋白 国家对照品 蛋白质含量 辛酸钠 多聚体 钠离子含量 乙酰色氨酸含量 

分 类 号：Q512.1[生物学—生物化学]