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以LC-ESI-HRMS为基础评估抗氧化剂作为抑制基因毒胺形成的添加剂

Aishwarya Dande¹, Nikhil Pallaprolu¹, Sangita Gadilohar¹

¹Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER)-Hajipur, Bihar, 844102, India.

AAPS PharmSciTech

|August 21, 2025

概括

像特洛克斯这样的抗氧化剂显著降低了甲福林片中有害的尼托胺 (NDMA) 的形成. 这种配方策略还提高了药物的生物可用性,并最大限度地减少了DNA损伤,从而提高了甲胺的安全性.

科学领域:

制药科学
药物安全
化学分析

背景情况:

尼胺,如N-尼二甲基胺 (NDMA),是基因毒性和致癌杂质.
在化条件下,化甲 (MET) 片中的NDMA形成已知问题.
抗氧化剂在MET片中缓解NDMA形成的作用尚未得到充分证实.

研究的目的:

评估抗氧化剂 (特洛克斯,酸,α-托科菲罗尔) 在减少MET片中的NDMA形成方面的有效性.
评估抗氧化剂对MET生物可用性和基因毒性的影响.
探索一种基于配方的方法来控制药品中的尼胺杂质.

主要方法:

含有或不含抗氧化剂 (特洛克斯,酸,α-托科菲罗尔) 和酸盐的MET片的配方.
在加快和长期条件下的稳定性研究为期三个月.
使用LC-HRMS,体外Caco-2透性试验和体外彗星基因毒性试验量化NDMA.

主要成果:

在压力条件下,抗氧化剂显著减弱了MET片中的NDMA形成.
在加速储存的过程中,Trolox (5%) 显示出最大的NDMA抑制 (62. 16%).
托洛克斯增强了MET传输 (2. 17倍) 并有效减少了NDMA诱导的DNA损伤.

结论:

加入抗氧化剂是控制MET片中的NDMA形成的一种可行的策略.
在减轻尼托拉胺风险和改善药物的生物可用性方面,Trolox具有显著的潜力.
这种配方方法为增强含有甲胺的药物安全提供了有希望的解决方案.

关键词:

NDMA 公司抗氧化剂生物可用性彗星测试甲福明化物

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