自从他们发现含有缬沙坦的药物以来,亚硝胺杂质已成为药品中的一个重大安全问题,促使广泛召回和暂停。缬沙坦,坎地沙坦,厄贝沙坦,奥美沙坦,和其他sartans已被发现含有额外的亚硝胺杂质,如N-亚硝基-N-甲基-4-氨基丁酸(NMBA),N-亚硝基二异丙胺(NDIPA),N-亚硝基乙基异丙基胺(NEIPA),和N-亚硝基二乙胺(NDEA)。对药物安全性的担忧与日俱增,以回应药品中亚硝胺污染的报道,如吡格列酮,利福平,利福喷丁,和伐尼克林。这篇综述调查了亚硝胺和药品中亚硝胺杂质的发生和影响,以及它们的根本原因。讨论强调了在药物开发和制造的各个阶段进行全面风险评估和缓解方法的重要性。还研究了胺和亚硝胺杂质之间的联系,强调pH值和初级的行为,次要,第三级,和季胺。定义亚硝胺评估和管理标准的法规,如ICHQ3A-Q3E和ICHM7,是解决杂质问题的关键。此外,强调全球物质注册系统(GSRS)对于制药行业的信息共享和产品安全至关重要。在亚硝胺污染对患者安全和药物供应的影响的背景下,该综述特别关注雷尼替丁与N-亚硝基二甲胺(NDMA)之间的关系。强调了监管机构在发现和纠正亚硝胺杂质方面的重要性,以提高患者安全性,产品质量,和预期寿命。此外,强调了正在进行的研究和关注亚硝胺相关影响对提高药物安全性和整体公共卫生的重要性.
Since their discovery in valsartan-containing drugs, nitrosamine impurities have emerged as a significant safety problem in pharmaceutical products, prompting extensive recalls and suspensions. Valsartan, candesartan, irbesartan, olmesartan, and other sartans have been discovered to have additional nitrosamine impurities, such as N-nitroso-N-methyl-4-aminobutyric acid (NMBA), N-nitroso-Di-isopropyl amine (NDIPA), N-nitroso-Ethyl-Isopropyl amine (NEIPA), and N-nitroso-Diethyl amine (NDEA). Concerns about drug safety have grown in response to reports of nitrosamine contamination in pharmaceuticals, such as pioglitazone, rifampin, rifapentine, and varenicline. This
review investigates the occurrence and impact of nitrosamine impurities in sartans and pharmaceutical goods, as well as their underlying causes. The discussion emphasizes the significance of comprehensive risk assessment and mitigation approaches at various phases of medication development and manufacturing. The link between amines and nitrosamine impurities is also investigated, with an emphasis on pH levels and the behaviour of primary, secondary, tertiary, and quaternary amines. Regulations defining standards for nitrosamine assessment and management, such as ICH Q3A-Q3E and ICH M7, are critical in resolving impurity issues. Furthermore, the Global Substance Registration System (GSRS) is underlined as being critical for information sharing and product safety in the pharmaceutical industry. The
review specifically focuses on the relationship between ranitidine and N-nitroso dimethyl amine (NDMA) in the context of the implications of nitrosamine contamination on patient safety and medicine supply. The importance of regulatory authorities in discovering and correcting nitrosamine impurities is highlighted in order to improve patient safety, product quality, and life expectancy. Furthermore, the significance of ongoing study and attention to nitrosamine-related repercussions for increasing pharmaceutical safety and overall public health is emphasized.