制药产品N-尼胺形成途径的预测
Genichiro Tsuji1, Takashi Kurohara1, Takuji Shoda1
1National Institute of Health Sciences.
Chemical & pharmaceutical bulletin
|January 31, 2024
概括
预测制药中的N-尼托胺污染是非常重要的. 这项研究使用了in silico软件来预测和确认从药物降解中产生的N-二甲基胺 (NDMA) 的形成,有助于高质量的制药生产.
科学领域:
- 制药化学 制药化学 的相关文章
- 药品安全 药品安全
- 分析化学 分析化学
背景情况:
- 制药中的N-二甲基胺 (NDMA) 污染对药物供应和患者安全构成重大风险.
- 鉴定和减轻突变性N-尼托拉胺的来源对于药品质量控制和监管合规至关重要.
研究的目的:
- 使用in silico方法预测药品中潜在的N-尼托胺污染.
- 实验验证从特定药物降解产品中形成N-尼托胺的途径.
- 评估专家知识软件对N-尼托胺形成风险评估的有用性.
主要方法:
- 使用专家知识软件,对gliclazide和indapamide的降解途径和杂质进行in silico预测.
- 在不同的条件下使用过氧化进行预测N-尼托拉胺形成的实验验证.
- 使用兰尼蒂丁作为参考化合物对NDMA形成途径的研究.
主要成果:
- 在 silico 预测中准确地确定了gliclazide 和 indapamide 的潜在 N-nitrosamine 形成.
- 演示性测试证实了这些药物产生的N-尼托胺,特别是在过氧化的性条件下.
- 拉尼蒂丁的分析表明,一个相关的化合物是NDMA的尼特罗斯基的来源.
结论:
- In silico软件是预测药品中N-尼托胺污染风险的宝贵工具.
- 了解降解途径有助于防止DNA反应杂质的形成.
- 这种方法支持开发生产更安全,高质量的药品的战略.
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