元素杂质是关乎药品质量重要的因素之一。合理控制药品中元素杂质也成为了业界关注的重点。国际人用药物注册技术协调会（ICH） Q3D明确了药品中可能残留的元素杂质的类型及其限度，这也为药品的开发和生产指明了方向。然而，元素杂质种类繁多，向药物中引入途径复杂，这为科学评估药品中元素杂质的安全性带了极大挑战。在众多的元素杂质引入途径中，原料药的制备工艺可能使用多种类型金属催化剂或无机试剂，这无疑是造成药品中元素杂质残留最为重要的影响因素。因此全面认识和理解不同元素以何种形式参与原料药的生产是科学控制元素杂质的关键。按照ICH Q3D汇总的3类元素杂质为序，介绍了不同金属在原料药合成中参与的反应。同时，建议将“质量源于设计”理念植入到原料药的生产工艺中，确保元素杂质水平符合《中国药典》和指导原则要求。

The elemental impurities are closely associated with the quality of drugs. Control of the elemental impurities has become one of the focuses of attention for industy. ICH Q3D guidance had determined the types of the elemental impurities and corresponding limits. This also points out the direction for the development and production of drug. Although, due to the wide varieties and complex of introduction way, it is with great challenge for scientifically estimating the safety of the elemental impurities. Among all introduction ways, different metal catalysts and inorganic reagents were often used in the production of drugs. This is undoubtedly vital factor resulting in the elemental impurities residue. Therefore, the key for scientifically controlling the elemental impurities is that comprehensive understand and know their participation modes in drugs production. According to the three types of the elemental impurities ICH Q3D summarized, this paper introduced the metal-mediated reactions in the process of drug synthesis. Meanwhile, it is recommended that the concept of "Quality by Design" be implanted into the production process of the drug substance to ensure that the level of elemental impurities meets the requirements of the Pharmacopoeia of the People's Republic of China and guidelines.

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