³H和¹⁴C标记药物的制备及其质量控制

³H和¹⁴C标记药物广泛应用于新药研究和药物残留分析等领域，是用来阐明药物代谢、处置过程及评价药物残留危害的完美工具。³H和¹⁴C标记药物还可用于研究物质的生物化学特性，揭示生物合成途径和酶促反应机制，阐明有机反应机制和解决环境科学领域诸多问题。放射性示踪研究可提供化合物分子及其分解产物、代谢产物、相关物质的定量信息，在新药或待开发药物的药理学与毒理学研究中，拥有不可代替的作用，是利用大部分药物分子中含有H或C原子的特点，用适当标记制备方法，将药物分子中原有的H或C原子用³H或¹⁴C等放射性原子替代，用于后续放射性示踪研究的一种特殊手段。³H和¹⁴C标记药物的制备包括选择、评估和优化放射性标记合成路线和工艺；挑选合适的³H和¹⁴C前导物及中间体；常规合成规模改造成微量合成规模；优化反应条件和收率；最后还要进行放射性标记化合物的结构确证，分析测量其化学纯度、放化纯度、比活度和标记位置以及相关质量控制项目。由于³H和¹⁴C标记药物对药物研发领域的重大影响，本文采用举例讨论方法，对³H和¹⁴C标记药物的制备策略、技术路线选择、合成方法、微量合成改造及其质量控制技术进行了较为详细的论述。

³H and ¹⁴C labeled compounds are excellent investigative tools and widely used to carry out drug metabolism and disposition studies during drug discovery and development stages,and risk evaluation of drug residues.Compounds labeled with ¹⁴C or ³H also have contributed to numerous advances in studies of biochemistry,biosynthetic pathways,enzyme mechanisms,elucidation of organic reaction mechanisms and environmental sciences.The use of radioactivity offers a unique mode of quantitative information of total drug-related molecules,and their decomposition products,metabolites and other substances.Therefore,most of the relevant studies that carry out radioactive tracers use ³H or ¹⁴C instead of H or C of original drug molecules.The preparation of compounds labeled with ³H and ¹⁴C usually involves the design of the preparation,method and apparatus for the identification and characterization of the labeled compounds.Therefore the planning process for syntheses of ³H and ¹⁴C labeled compounds involves evaluation of synthetic pathways,selection of building blocks,modification of microscale synthesis methods,identification of the labeled compounds,analysis of the chemical purity,radiochemical purity,specific activity and position of label.Due to the significant impact of ³H and ¹⁴C labeled compounds on applications in the drug research,this study described strategies for target preparation,preparation of ³H and ¹⁴C labeled compounds and quality control methods of the ³H and ¹⁴C labeled compounds.