Zhao Xinyu, Li Caixia, Zeng Hongxia, Gu Xiao, Zheng Jinqi
Zhejiang University of Technology, Hangzhou 310014, China.
Zhejiang Institute for Food and Drug Control, Hangzhou 310052, China; Key Laboratory for Core Technology of Generic Drug Evaluation National Medical Product Administration, Key Laboratory of Drug Contacting Materials Quality Control of Zhejiang Provincial, Hangzhou 310052, China.
J Pharm Biomed Anal. 2024 Sep 15;248:116274. doi: 10.1016/j.jpba.2024.116274. Epub 2024 Jun 4.
There is an increasing scientific interest in the detection of genotoxic impurities (GTIs), with nitrobenzene compounds being considered potential genotoxic impurities due to their structural alerts, which demonstrates a threat to drug safety for patient. While current reports on the detection of nifedipine impurity primarily focus on general impurities in nifedipine. In this study, an effective and simple gas chromatography-mass spectrometry (GC-MS) method was established and verified for the separation and quantification of 2-nitrotoluene, 2-nitrobenzyl alcohol, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, and 2-nitrobenzyl bromide in nifedipine, which have not been previously reported. The validation of this GC-MS method was conducted following the International Conference of Harmonization (ICH) guidelines, exhibiting good linearity within the range of 2-40 μg/g and accuracy between 84.6 % and 107.8 %, the RSD% of intra-day and inter-day precision was in the range of 1.77-4.55 %, stability and robustness also met acceptance criteria. This method filled the gap in detection method for nitrobenzene compounds in nifedipine, offering a novel method and technical support for nifedipine quality control.
对遗传毒性杂质（GTIs）的检测，科学界的关注度日益增加，由于其结构警示，硝基苯化合物被视为潜在的遗传毒性杂质，这对患者的药物安全构成威胁。虽然目前关于硝苯地平杂质检测的报告主要集中在硝苯地平中的一般杂质上。在本研究中，建立并验证了一种有效且简单的气相色谱 - 质谱联用（GC-MS）方法，用于分离和定量硝苯地平中的2-硝基甲苯、2-硝基苯甲醇、2-硝基苯甲醛、3-硝基苯甲醛、4-硝基苯甲醛和2-硝基苄基溴，这些此前未见报道。该GC-MS方法按照国际协调会议（ICH）指南进行验证，在2 - 40μg/g范围内呈现良好的线性，准确度在84.6%至107.8%之间，日内和日间精密度的相对标准偏差（RSD%）在1.77 - 4.55%范围内，稳定性和耐用性也符合验收标准。该方法填补了硝苯地平中硝基苯化合物检测方法的空白，为硝苯地平质量控制提供了新方法和技术支持。
