摘要
目的建立ICP-MS同时测定药用辅料结晶氯化铝中14种元素杂质含量的方法,并进行风险评估。方法采用电感耦合等离子体质谱内标法。以Te、Sc、Ge、In、Bi元素为内标,采用标准加入法,样品稀释后直接进样,测定8批次样品中14种元素杂质的含量(包括1类元素:Cd、Pb、As、Hg;2A类元素:Co、V、Ni;3类元素:Li、Sb、Ba、Mo、Cu、Sn、Cr)。并根据ICH Q3D对口服、注射、吸入3种给药途径对元素的每日允许暴露量进行风险评估。结果各元素在相应的浓度范围内均具有良好的线性关系(r≥0.9993),精密度试验RSD<4.3%,重复性试验RSD<7.8%,加样回收率在93.9%~111.9%,RSD为2.3%~7.8%(n=9)。Ni、V、Li、Cr 4种元素在少数样品中高于相应吸入方式的每日允许暴露量,均低于注射及口服方式。结论该方法简便、快速、准确,可同时测定结晶氯化铝中的元素杂质。依测定结果提示使用企业应关注辅料的实际用途及特定的给药途径,辅料生产企业应进行必要的原料筛选、过程控制与工艺改进。
OBJECTIVE To establish a method for simultaneously determining the content of 14 elemental impurities in the aluminum chloride hexahydrate and to conduct a risk assessment.METHODS An internal standard method using inductively coupled plasma mass spectrometry was employed.Elements Te,Sc,Ge,In,and Bi were used as internal standards.The standard addition method was applied,with samples diluted and directly injected.The contents of 14 elemental impurities in 8 batches of samples were determined(including Class 1 elements:Cd,Pb,As,Hg;Class 2A elements:Co,V,Ni;Class 3 elements:Li,Sb,Ba,Mo,Cu,Sn,Cr).A risk assessment was conducted based on the ICH Q3D guidelines for the permitted daily exposure(PDE)of these elements for oral,injectable,and inhalation routes of administration.RESULTS Each element demonstrated a good linear relationship within the respective concentration range(r≥0.9993).The precision test had an RSD of less than 4.3%,the repeatability test had an RSD of less than 7.8%,and the spike recovery rate ranged from 93.9%to 111.9%,with an RSD of 2.3%to 7.8%(n=9).Elevated levels of Ni,V,Li,and Cr were observed in a subset of samples,exceeding the inhalation PDE limits but remaining within the safer limits established for injectable and oral administration.CONCLUSION This method is simple,rapid,and accurate,and can be used for the simultaneous determination of elemental impurities in crystalline aluminum chloride.Enterprises should pay attention to the actual use of excipients and specific routes of administration.Excipient manufacturers should undertake necessary raw material screening,process control,and process improvements.
作者
赵璇
纪宏
冯建杰
李文东
段艳
ZHAO Xuan;JI Hong;FENG Jianjie;LI Wendong;DUAN Yan(Beijing Institute for Drug Control(Beijing Center for Vaccine Control),NMPA Center for Innovation and Research in Regulatory Science,Beijing 102206,China)
出处
《中国现代应用药学》
北大核心
2026年第1期102-108,共7页
Chinese Journal of Modern Applied Pharmacy
基金
2023年国家药品标准制修订研究课题(2023Y033)。
