ICP-MS法测定硫酸沙丁胺醇吸入气雾剂中20种元素杂质  

Determination of 20 elements impurities in Salbutamol Sulfate Inhalation Aerosol by ICP-MS

作　　者：张连义 陈真 刘中原 牛冲 李文馨 郑静 窦艳丽 郭常川 刘琦 徐玉文 ZHANG Lianyi;CHEN Zhen;LIU Zhongyuan;NIU Chong;LI Wenxin;ZHENG Jing;DOU Yanli;GUO Changchuan;LIU Qi;XU Yuwen(NMPA Key Laboratory for Research and Evaluation of Generic Drugs,Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs,Shandong Institute for Food and Drug Control,Jinan 250101,China;Shandong Pharmacists Association,Jinan 250101,China)

机构地区：[1]山东省食品药品检验研究院,国家药品监督管理局仿制药研究与评价重点实验室,山东省仿制药一致性评价工程技术研究中心,山东济南250101 [2]山东省药师协会,山东济南250101

出　　处：《药学研究》2025年第3期241-245,295,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金项目(No.81573606、81973486);泰山产业领军人才工程专项经费(No.tscx202306073)。

摘　　要：目的建立电感耦合等离子体质谱法(ICP-MS)测定硫酸沙丁胺醇吸入气雾剂中无机元素杂质的方法,并对国家药品抽检样品进行评价。方法根据ICH指导原则Q3D(R2)元素杂质指导原则中元素分类,并进行半定量全扫描分析,确定待分析元素的类型,包括20种元素:Li、B、Si、Al、Ti、V、Cr、Co、Ni、Cu、Zn、As、Mo、Cd、Sn、Sb、Ba、Au、Hg、Pb;采用内标校正的标准曲线法进行测定。结果建立的内标校正的曲线法能够准确测定各杂质线性范围内的元素杂质含量,相关系数r大于0.999。4家企业的抽检样品中,1类元素Pb在企业a、c、d中检出均值在0.02~0.03 ng·mL^(-1),最大值0.054 ng·mL^(-1)。其他1类元素Cd、Hg、As未检出。2A类元素Co、V未检出,元素Ni检出均值在0.2~0.5 ng·mL^(-1)。3类元素Sb、Ba、Mo、Sn未检出。元素Li、Cu、Cr微量检出,元素Li均值在0.10~0.13 ng·mL^(-1),元素Cu均值在0.2~0.4 ng·mL^(-1)。元素Cr均值在0.11~1.5 ng·mL^(-1)。半定量筛选的元素中,元素B、Al、Si、Zn均大量检出。结论该方法灵敏、准确、简便,可有效测定硫酸沙丁胺醇吸入气雾剂中的无机元素杂质。Objective To establish an inductively coupled plasma mass spectrometry(ICP-MS)method for the determination of inorganic element impurities in Salbutamol Sulfate Inhalation Aerosol,and application in national drug sampling samples.Methods According to the ICH guiding principle Q3D(R2):Guideline for Elemental Impurities and semi-quantitative analysis,the types of elements to be analyzed were determined,including 20 elements:Li,B,Si,Al,Ti,V,Cr,Co,Ni,Cu,Zn,As,Mo,Cd,Sn,Sb,Ba,Au,Hg,Pb;The internal standard correction standard curve method was used for determination.Results The established internal standard calibration curve method was able to accurately determine the assay of elemental impurities within the linear range of each impurity,and the linear correlation coefficients were all higher than 0.999.Among the sampled samples from four enterprises,the average detection value of Class 1 element Pb in enterprises a,c,and d ranges from 0.02 to 0.03 ng·mL^(-1),with a maximum value of 0.054 ng·mL^(-1).Other Class 1 elements Cd,Hg,and As were not detected.Class 2A elements Co and V were not detected,while the average detection of element Ni ranged from 0.2 to 0.5 ng·mL^(-1).Three types of elements Sb,Ba,Mo,and Sn were not detected.Trace amounts of elements Li,Cu,and Cr were detected,with an average of 0.10~0.13 ng·mL^(-1)for element Li and 0.2~0.4 ng·mL^(-1)for element Cu.The average value of element Cr ranges from 0.11 to 1.5 ng·mL^(-1).Among the elements selected for semi-quantitative analysis,a large amounts of elements B,Al,Si,and Zn were detected.Conclusion The established method is sensitive,accurate,simple,can effectively determine the inorganic element impurities in salbutamol sulfate inhalation aerosol.

关 键 词：硫酸沙丁胺醇吸入气雾剂 电感耦合等离子体质谱法 包材相容性 元素迁移 无机元素杂质 

分 类 号：R927.1[医药卫生—药学]