那屈肝素钙中N-NO的去除方法研究  

Removal Method of N-NO in Nadroparin Calcium

作　　者：郑华淦 廖冬 曲和之 ZHENG Huagan;LIAO Dong;QU Hezhi(Shenzhen Sciprogen Bio-Pharmaceutical Co.,Ltd.,Shenzhen 518129,China)

机构地区：[1]深圳赛保尔生物药业有限公司,广东深圳518129

出　　处：《化学与生物工程》2024年第2期65-68,共4页Chemistry & Bioengineering

基　　金：深圳市工信局扶持项目(20200619145347736)。

摘　　要：分别采用氧化法、加热法、微波照射法、紫外照射法处理那屈肝素钙粗品,比较了不同方法对N-NO的去除效果;并进一步研究了紫外照射时间对那屈肝素钙产品关键指标的影响,进行了3批工艺验证和N-NO含量测定的方法学验证。结果表明,氧化法、加热法、微波照射法仅能去除50%左右的N-NO,而紫外照射20~60 min可以去除95%以上的N-NO,使那屈肝素钙产品符合欧洲药典(EP)标准要求(N-NO含量≤0.25μg·g^(-1));紫外照射对那屈肝素钙产品的分子量、效价等关键指标无影响;方法学验证结果表明,热能分析仪适用于那屈肝素钙中N-NO含量的测定。We treated the crude Nadroparin Calcium by oxidation method,heating method,microwave irradiation method,and UV irradiation method,and compared the the removal effects of N-NO by different methods.Meanwhile,we further studied the influence of UV irradiation time on the key indexes of Nadroparin Calcium products,and carried out three batches of process validation and methodology verification for determination of N-NO content.The results show that only about 50%of N-NO can be removed by oxidation method,heating method,and microwave irradiation method,while more than 95%of N-NO can be removed by UV irradiation for 20-60 min,which can enable Nadroparin Calcium products to meet the European Pharmacopoeia(EP)standard(N-NO content≤0.25μg·g^(-1)).UV irradiation has no effect on the molecular weight,potency and other key indexes of Nadroparin Calcium products.The results of methodology verification show that the thermal energy analyzer is suitable for the determination of N-NO content in Nadroparin Calcium.

关 键 词：那屈肝素钙 N-NO 亚硝胺 紫外照射 效价 热能分析仪 

分 类 号：R973[医药卫生—药品]