Abstract：
This study assessed the presence of the genotoxic impurity 1-methyl-4-nitrosopiperazine (MNP) in 27 batches of rifampicin capsules obtained from 11 manufacturers in China. While they were below the temporary limit of 5 ppm set by the US Food and Drug Administration, the observed levels (0.33-2.36 ppm) exceeded the acceptable threshold of 0.16 ppm. Building upon preliminary findings and degradation experiments, we concluded that MNP is a by-product of the oxidative degradation of rifampicin or is introduced via oxidation or nitrosation during the synthesis process involving 1-methyl-4-aminopiperazine. The pathways of MNP formation were confirmed in this study. Furthermore, we observed that the addition of antioxidants, sealed storage, and selection of dominant crystal forms can aid in controlling MNP levels.
摘要：
这项研究评估了从中国11家制造商获得的27批利福平胶囊中遗传毒性杂质1-甲基-4-亚硝基哌嗪（MNP）的存在。虽然它们低于美国食品和药物管理局设定的5ppm的临时限值，观察到的水平（0.33-2.36ppm）超过了0.16ppm的可接受阈值。在初步发现和降解实验的基础上，我们得出的结论是，MNP是利福平氧化降解的副产物，或者是在涉及1-甲基-4-氨基哌嗪的合成过程中通过氧化或亚硝化引入的。本研究证实了MNP形成的途径。此外，我们观察到添加抗氧化剂，密封存储,和选择主导晶体形式可以帮助控制MNP水平。
