磺胺二甲嘧啶有关杂质国家标准物质的研制

Establishment of National Reference Standards of Sulfadimidine Impurities

目的介绍磺胺二甲嘧啶有关杂质的国家标准物质研制过程,为提高我国磺胺二甲嘧啶质量控制标准提供保障。方法首先采用红外、质谱和核磁共振方法,对磺胺二甲嘧啶杂质A、E进行结构确认,然后采用《欧洲药典》(9. 0版)磺胺二甲嘧啶有关物质检查方法测定杂质A和E的纯度,同时测定磺胺二甲嘧啶杂质A、E的水分和炽灼残渣含量,应用质量平衡法确定首批磺胺二甲嘧啶杂质A和E国家标准物质的含量。同时还采用外标法和核磁定量方法测定其含量,与质量平衡法相互验证。最后采用标准曲线法测定了磺胺二甲嘧啶杂质A、E对磺胺二甲嘧啶在241 nm检测波长下的校正因子。结果磺胺二甲嘧啶杂质A、E与《欧洲药典》规定的结构相同,质量平衡法测定杂质A、E的含量分别为99. 1%和98. 7%,与外标法和核磁定量的结果基本一致,杂质A和E对磺胺二甲嘧啶的较正因子分别为0. 97和0. 63。结论建立了首批磺胺二甲嘧啶杂质A、E的国家标准物质。

OBJECTIVE To establish the national reference standards of sulfadimidine impurities thus to provide guarantee for improving the standard of quality control of sulfadiazine in China. METHODS First,the structures of sulfadimidine impurities A and E were validated by infrared spectrocopy,mass spectrum and nuclear magnetic resonance method. Then,the purities of impurities A and E were determined using the method of related substance test for sulphadiazine in the European Pharmacopoeia( version 9. 0),their water content and residue on ignition were determined as well. The contents of sulfadimidine impurities A and E were determined by using mass balance method. Meanwhile,external standard method and nuclear magnetic quantitative method were used to calculate the content,which were mutually verified with the mass balance method. Finally,the correction factors of sulfadiazine impurities A and E at 241 nm were determined using standard curve method. RESULTS The structures of sulfadimidine impurities A and E were confirmed,and the contents of impurities A and E were 99. 1% and 98. 7%,respectively,which were calculated by mass balance method. The results were consistent with those obtained from external standard method and nuclear magnetic quantification method. The correction factors of impurities A and E to sulfadimidine were 0. 97 and 0. 63,respectively. CONCLUSION The first batch of national standard substances of sulfadimidine impurities A and E were established successfully.