中国药物警戒 ›› 2025, Vol. 22 ›› Issue (1): 53-57.
DOI: 10.19803/j.1672-8629.20240572

• 放射性药品监管科学研究专栏 • 上一篇    下一篇

ICP-MS测定注射用亚锡二巯丁二钠中15种元素杂质含量

姚静1, 连晓芳2,∆, 左利民2, 郭鑫2, 刘惠一2, 谷永升2,3, 贾庆莹2, 黄海伟1,*   

  1. 1中国食品药品检定研究院化学药品检定所,北京 102629;
    2中国医学科学院医药生物技术研究所,北京 100050;
    3新疆医科大学药学院,新疆 乌鲁木齐 830017
  • 收稿日期:2024-08-12 出版日期:2025-01-15 发布日期:2025-01-22
  • 通讯作者: *黄海伟,男,本科,副主任药师,药物分析。E-mail: huanghw@nifdc.org.cn
  • 作者简介:姚静,女,博士,副主任药师,药物分析。△为并列第一作者。
  • 基金资助:
    国家科技重大专项重大新药创制（2017zx091010 01）; 中国食品药品检定研究院关键技术研究基金（GJJS-2022-4-1）

Determination of Contents of 15 Elemental Impurities in Kits of Dimercaptosuccinate Acid and Stannous Chloride for Injection by ICP-MS

YAO Jing1, LIAN Xiaofang2,∆, ZUO Limin2, GUO Xin2, LIU Huiyi2, GU Yongsheng2,3, JIA Qingying2, HUANG Haiwei1,*   

  1. 1Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing 102629, China;
    2Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China;
    3College of Pharmacy, Xinjiang Medical University, Urumqi Xinjiang 830017, China
  • Received:2024-08-12 Online:2025-01-15 Published:2025-01-22

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摘要： 目的 建立测定注射用亚锡二巯丁二钠中元素杂质的电感耦合等离子体质谱（Inductively Coupled Plasma-Mass Spectrometry,ICP-MS）方法。方法 使用ICP-MS半定量测定模式对注射用亚锡二巯丁二钠中元素杂质进行筛查,结合人用药品技术要求国际协调理事会（ICH）Q3D元素杂质指导原则的要求,确定15种元素：锂（Li）、铝（Al）、钾（K）、钒（V）、铁（Fe）、钴（Co）、镍（Ni）、铜（Cu）、锌（Zn）、砷（As）、镉（Cd）、铟（In）、锑（Sb）、汞（Hg）和铅（Pb）作为定量考察和控制的元素杂质研究对象。ICP-MS采集模式选择动能歧视（Kinetic Energy Discrimination,KED）模式,分别以钪（Sc）、锗（Ge）、钇（Y）、铋（Bi）作为内标,采用重复采样3次的平均值报告结果。结果 经元素筛查发现注射用亚锡二巯丁二钠中存在相对较高的Al、K、Fe、Zn、In 5种元素。不同企业产品元素杂质含量测定结果显示出一定的生产商分布特点。建立的定量方法验证显示,15种元素杂质在各自线性范围内响应与浓度相关性良好（r>0.991 7）;方法精密度（RSD≤3.72%）和重复性（RSD≤3.53%）满足测定要求;各元素平均回收率93.45%~105.38%（RSD≤4.28%,n=9）,方法准确性良好。结论 金属盐类制剂产品可能引入ICH Q3D元素杂质指导原则要求以外的元素杂质。本研究建立的ICP-MS定量方法简便、快速,可用于注射用亚锡二巯丁二钠中元素杂质的筛查、检测和风险评估。

关键词: 亚锡二巯丁二钠, 注射用, 元素杂质, 半定量筛查, 电感耦合等离子体质谱法, 定量分析

Abstract: Objective To establish an inductively coupled plasma mass spectrometric (ICP-MS) method for the determination of elemental impurities in kits of dimercaptosuccinate acid and stannous chloride for injection. Methods The elements in kits of dimercaptosuccinate acid and stannous chloride for injection were screened using ICP-MS in a semi-quantitative mode. The elemental impurities were determined before being examined and controlled as required by the ICH Q3D guidelines for elemental impurities. There were 15 elements: Li, Al, K, V, Fe, Co, Ni, Cu, Zn, As, Cd, In, Sb, Hg and Pb, which were chosen as the subjects. The kinetic energy discrimination (KED) mode was selected for ICP-MS while Sc, Ge, Y and Bi were used as the internal standards. The sampling was repeated three times to determine the average value. Results The contents of five elements-Al, K, Fe, Zn and In-were found to be relatively high in the kit of dimercaptosuccinate acid and stannous chloride for injection after elemental screening. The results of determination of elemental impurities of products by different enterprises revealed characteristics of distribution. Methodological validation indicated that the impurities of each element were within the linear range and correlated (r >0.991 7), and that the precision (RSD≤3.72%) and reproducibility (RSD≤3.53%) of the method met the requirements, with the average recoveries of these elements ranging from 93.45% to 105.38% (RSD≤4.28%, n=9), and the accuracy was good. Conclusion Metal salts may introduce impurities of elements other than those required by ICH Q3D guidelines. The method established in this study is simple, rapid and can meet the requirements for the detection and risk evaluation of elemental impurities in the kit of dimercaptosuccinate acid and stannous chloride for injection.

Key words: Kit of Dimercaptosuccinate Acid and Stannous Chloride, Injection, Elemental Impurities, Semi-quantitative Screening, Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Quantitative Analysis

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