摘要
目的:为满足国内重组特立帕肽(重组人甲状旁腺激素1-34,rh PTH1-34)及相关制剂质量控制的需要,研制并标定首批重组特立帕肽国家标准品。方法:采用免疫斑点、质谱、N端氨基酸测序、反相HPLC鉴别、氨基酸组成以及肽图等方法对用于待标品制备的原液进行定性及结构确认;以WHO第2批rhPTH1-34国际标准品15/304作为标准,参照原国家食品药品监督管理总局颁发的生物制品标准YBS00062017中相关方法,联合3个实验室参加协作标定;并对待标品均一性及稳定性进行考察。结果:重组特立帕肽待标品经协作标定,最终含量定值为0.975 mg·瓶^(-1),生物效价为9750 IU·瓶^(-1);均一性考察符合要求、稳定性考察结果4℃条件下20 d纯度略有下降,40℃放置5 d和光照20 d后纯度明显下降。结论:本批待标品确认为重组特立帕肽,可以作为首批重组特立帕肽国家标准品,以供重组特立帕肽及相关制剂的HPLC鉴别、含量测定及生物活性测定用,本批待标品含量以0.975 mg·瓶^(-1)计,效价以9750 IU·瓶^(-1)计。
Objective:To fulfill the requirement of quality control on recombinant teriparatide(parathyroid hormone 1-34,rhPTH1-34)and related drug products in domestic,the 1^(st)batch of national standard(NS)was prepared and calibrated in this study.Methods:The structure of candidate preparation concentrate was confirmed by dot immunobinding assay(DIBA),MS,N-terminal sequencing,RP-HPLC identification,amino acid composition and peptide mapping.Taking the 2^(nd)WHO international standard 15/304 as the reference standard,the 1st batch NS of rh PTH1-34 was calibrated,respectively,by 3 laboratories using the in vitro bioassay in YBS00062017 standard approved by CFDA.Thermal stability and uniformity test for the candidate preparation were carried out.Results:The biopotency of the 1st batch NS candidate of rh PTH1-34 for content determination and bioassay was evaluated to be 9750 IU per vial,content was 0.975 mg per vial.Thermal stability and uniformity test were qualified.The uniformity met the requirement.The purity decreased slightly at 4℃in 20 d,decreased significantly at 40℃in 5 d and exposure under light in 20 d.Conclusions:The candidate preparation was confirmed to be rhPTH1-34 and can serve as the 1^(st)batch NS recombinant teriparatide which can be used for HPLC identification,content determination as well as bioassay.Each vail contains 9750 IU PTH,equivalent to 0.975 mg per vail.
作者
张伟
张慧
吕萍
李晶
陈莹
王绿音
李懿
汤火龙
黄洁
梁成罡
ZHANG Wei;ZHANG Hui;Lü Ping;LI Jing;CHEN Ying;WANG Lü-yin;LI Yi;TANG Huo-long;HUANG Jie;LIANG Cheng-gang(National Institutes for Food and Drug Control,Beijing 102629,China;Shanghai United Cell Biotechnology Co.,Ltd.,Shanghai 201206,China;Salubris-SZ Pharmaceuticals Co.,Ltd.,Suzhou 215425,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2021年第7期654-659,共6页
Chinese Journal of New Drugs
