自2018年以来，N-亚硝胺杂质已成为全球药品监管领域的广泛关注点。这种担忧的产生是因为它们具有潜在的污染、毒性、致癌性和致突变性，以及它们存在于许多活性药物成分、药品和其他基质中。 N-亚硝胺杂质在人体中会导致严重的化学毒性作用。这些包括致癌作用、代谢紊乱、生殖损害、肝脏疾病、肥胖、DNA 损伤、细胞死亡、染色体改变、出生缺陷和流产。尤其众所周知，它们会在各种器官和组织中引起癌症（肿瘤），例如肝脏、肺、鼻腔、食道、胰腺、胃、膀胱、结肠、肾脏和中枢神经系统。此外，N-亚硝胺杂质可能会导致阿尔茨海默病、帕金森病以及 2 型糖尿病的发生。因此，通过使用尖端分析技术（例如 LC-MS、GC-MS、CE-MS、SFC 等）增​​强有效的分析方法来控制或避免它们非常重要。此外，这些分析方法需要灵敏且可靠以适当的精度和准确度进行选择性，以便能够对药物中 N-亚硝胺杂质的实际含量进行适当的检测和定量。美国FDA、EMA、ICH、WHO等监管机构需要通过向药品生产商和申请人提供指导和定期更新来更加关注N-亚硝胺杂质的危害。同样，药品制造商应更加警惕，避免在制造过程中使用亚硝化剂和仲胺。不同的研究人员最近发表了许多评论文章，重点关注先前通报的产品中发现的 N-亚硝胺杂质，包括沙坦类、二甲双胍和雷尼替丁。在多种其他产品中也检测到了这些杂质。因此，本次审查旨在重点关注最近报道的含有 N-亚硝胺杂质的产品。这些产品包括利福平、尚匹克、法莫替丁、尼扎替丁、阿托伐他汀、布美他尼、伊曲康唑、代文、依那普利、普萘洛尔、赖诺普利、度洛西汀、利伐沙班、吡格列酮、格列酮、西洛他唑和舒尼替尼。

Since 2018, N-nitrosamine impurities have become a widespread concern in the global regulatory landscape of pharmaceutical products. This concern arises due to their potential for contamination, toxicity, carcinogenicity, and mutagenicity and their presence in many active pharmaceutical ingredients, drug products, and other matrices. N-Nitrosamine impurities in humans can lead to severe chemical toxicity effects. These include carcinogenic effects, metabolic disruptions, reproductive harm, liver diseases, obesity, DNA damage, cell death, chromosomal alterations, birth defects, and pregnancy loss. They are particularly known to cause cancer (tumors) in various organs and tissues such as the liver, lungs, nasal cavity, esophagus, pancreas, stomach, urinary bladder, colon, kidneys, and central nervous system. Additionally, N-nitrosamine impurities may contribute to the development of Alzheimer's and Parkinson's diseases and type-2 diabetes. Therefore, it is very important to control or avoid them by enhancing effective analytical methodologies using cutting-edge analytical techniques such as LC-MS, GC-MS, CE-MS, SFC, etc. Moreover, these analytical methods need to be sensitive and selective with suitable precision and accuracy, so that the actual amounts of N-nitrosamine impurities can be detected and quantified appropriately in drugs. Regulatory agencies such as the US FDA, EMA, ICH, WHO, etc. need to focus more on the hazards of N-nitrosamine impurities by providing guidance and regular updates to drug manufacturers and applicants. Similarly, drug manufacturers should be more vigilant to avoid nitrosating agents and secondary amines during the manufacturing processes. Numerous review articles have been published recently by various researchers, focusing on N-nitrosamine impurities found in previously notified products, including sartans, metformin, and ranitidine. These impurities have also been detected in a wide range of other products. Consequently, this review aims to concentrate on products recently reported to contain N-nitrosamine impurities. These products include rifampicin, champix, famotidine, nizatidine, atorvastatin, bumetanide, itraconazole, diovan, enalapril, propranolol, lisinopril, duloxetine, rivaroxaban, pioglitazones, glifizones, cilostazol, and sunitinib.