元素雜質(zhì)是關(guān)乎藥品質(zhì)量重要的因素之一。合理控制藥品中元素雜質(zhì)也成為了業(yè)界關(guān)注的重點(diǎn)。國(guó)際人用藥物注冊(cè)技術(shù)協(xié)調(diào)會(huì)（ICH） Q3D明確了藥品中可能殘留的元素雜質(zhì)的類型及其限度，這也為藥品的開(kāi)發(fā)和生產(chǎn)指明了方向。然而，元素雜質(zhì)種類繁多，向藥物中引入途徑復(fù)雜，這為科學(xué)評(píng)估藥品中元素雜質(zhì)的安全性帶了極大挑戰(zhàn)。在眾多的元素雜質(zhì)引入途徑中，原料藥的制備工藝可能使用多種類型金屬催化劑或無(wú)機(jī)試劑，這無(wú)疑是造成藥品中元素雜質(zhì)殘留最為重要的影響因素。因此全面認(rèn)識(shí)和理解不同元素以何種形式參與原料藥的生產(chǎn)是科學(xué)控制元素雜質(zhì)的關(guān)鍵。按照ICH Q3D匯總的3類元素雜質(zhì)為序，介紹了不同金屬在原料藥合成中參與的反應(yīng)。同時(shí)，建議將“質(zhì)量源于設(shè)計(jì)”理念植入到原料藥的生產(chǎn)工藝中，確保元素雜質(zhì)水平符合《中國(guó)藥典》和指導(dǎo)原則要求。

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.

R914