目的: 建立专属性强的稳定性指示方法（SIM）,用以检测来那度胺原料药有关物质,以便能够有效地检出稳定性考察中产生的降解杂质。方法: 参照ICH指南以及各监管机构要求,通过强降解试验对有关物质方法专属性进行考察。结果: 采用超高压液相建立的来那度胺原料药有关物质稳定性指示方法,快速灵敏且专属性强,能够检测到相应的降解杂质并具有良好的分离度;各降解条件质量守恒,含量与杂质总和在95%~105%;通过LCMS对主要的降解杂质进行了分子量测定,并推测出结构。结论: 本研究确认了来那度胺原料药有关物质方法的专属性,揭示了来那度胺原料药内在特性、降解途径以及主要的降解杂质,有助于确定包装和贮藏条件,为稳定性考察方案提供数据支持,并为制剂处方法设计提供前期参考。
Objective: To establish a highly specific stability indicator method (SIM) for detecting related substances in lenalidomide API, in order to effectively detect degradation impurities generated during stability testing. Methods: Referring to the ICH guideline and the requirements of various regulatory agencies, the method specificity of related substances was investigated through stress testing. Results: The SIM for related substances of lenalidomide API established by UPLC was fast, sensitive, and highly specific, capable of detecting degradation impurities and having good separation, Under various degradation conditions, mass balance had been established, with the sum of assay and total impurities ranging from 95% to 105%; This article also measured the molecular weight of the main degradation impurities using LCMS and inferred their structures. Conclusion: This study not only confirmes the specificity of the related substance method, but also reveals the inherent characteristics of lenalidomide API. The degradation pathway and main degradation impurities of lenalidomide API is clarified. It helps to determine packaging and storage conditions, provides data support for stability assessment plans, and provides preliminary reference for formulation study.
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