通过液体染色学-并联质谱法量化N-((2-异乙醇-4-yl) 甲基) -N-甲基胺的微量定量
Sarju Adhikari1, Chad Catbagan1, Gavin Carr1
1Gilead Sciences, Inc., Foster City, CA 94404, USA.
Journal of pharmaceutical and biomedical analysis
|November 21, 2025
概括
一种新的敏感方法检测到N-((2-异乙醇-4-yl) 甲基) -N-甲基胺 (NITMA),一个强大的致癌物质,在里托纳维尔. 这种经过验证的LC-MS/MS技术通过量化这种杂质的低水平来确保药物安全.
科学领域:
- 分析化学 分析化学
- 药品分析 药品分析
- 质谱测量质量谱测量
背景情况:
- 氨酸胺是强大的致癌物质,引发了健康问题.
- 在利托纳维尔药物产品中检测到N-((2-异硫-4-yl) 甲基) -N-甲基胺胺 (NITMA),一种酸胺杂质.
- 对于NITMA,严格的可接受摄入量限制需要高度敏感的量化方法.
研究的目的:
- 开发和验证一种灵敏的液体染色学-并联质谱法 (LC-MS/MS) 方法,用于NITMA检测和量化.
- 在加速条件下研究从其前体中NITMA的形成,以防止人工生成.
- 确保复杂的制药矩阵中的方法多功能性.
主要方法:
- 液体染色学-双重质谱学 (LC-MS/MS) 与气压化学电离 (APCI) 在正模式下.
- 多重反应监测 (MRM) 用于敏感和选择性的量化.
- 根据ICH Q2 ((R2) 准则进行验证,包括对选择性和定量限制的评估.
主要成果:
- 开发了一种多功能和灵敏的LC-MS/MS方法,用于在里托纳维尔药物和混合物中的NITMA量化.
- 该方法在存在API,杂质和辅助剂的情况下证明了足够的峰值选择性.
- 通过成功的验证,达到0.0225 ng/mL的量化极限,符合监管要求.
结论:
- 开发的LC-MS/MS方法适用于对NITMA的敏感和准确量化.
- 该方法支持对利托纳维尔产品中NITMA的风险评估策略.
- 这种分析方法有助于确保合规性和患者安全.
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