在Letermovir中分离,合成和识别降解的杂质
Yuzhu Chai1, Erlong Zhang2, Zhuoer Cai3
1School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China; Nanjing Chia-Tai Tianqing Pharmaceutical Company, Nanjing 210046, PR China.
Journal of pharmaceutical and biomedical analysis
|September 13, 2023
概括
在细胞巨乳病毒感染治疗的降解研究中发现了letermovir杂质. 合成了五种新的杂质,进行了表征,并评估了它们的毒理性质.
科学领域:
- 制药化学 制药化学 制药化学
- 药物降解研究 药物降解研究
- 不洁净性分析 (Impurity Profiling) 是一种分析方法.
背景情况:
- 莱特莫维尔是细胞巨乳病毒 (CMV) 感染的关键抗病毒药物,特别是在血液细胞移植接受者中.
- 由于其临床应用,确保Letermovir的纯度和安全性至关重要.
研究的目的:
- 在各种压力条件下 (氧化,热,光分解) 识别和描述由莱特莫维尔降解产生的杂质.
- 阐明这些新杂质的形成路径和合成路径.
- 评估与已确定杂质相关的潜在毒理风险.
主要方法:
- 在氧化,热和光解条件下对莱特莫维尔的降解研究.
- 通过高分辨率质谱 (HRMS),核磁共振 (NMR) 谱学和X射线晶体学来合成和阐明检测到的杂质的结构.
- 高性能液体染色学 (HPLC) 用于保留时间的确认.
- 使用ACD/Percepta软件进行体毒理学评估.
主要成果:
- 检测并量化了五种新的杂质,含量从未检测到 (ND) 到2.21%不等.
- 这些杂质的结构已成功合成并得到证实.
- 使用HPLC,对杂质的保留时间与商用Letermovir进行了验证.
- 为杂质提出了潜在的形成途径和合成策略.
- 通过计算方法评估了杂质的毒理概况.
结论:
- 这项研究成功地确定和描述了莱特莫维尔在降解过程中形成的五种新杂质.
- 了解这些杂质的形成和特性对于莱特莫维尔药物产品的质量控制和安全评估至关重要.
- 毒理学评估为风险评估提供初步数据,指导进一步的安全调查.
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