N-nitroso quinapril and N-nitroso ramipril are not genotoxic in vitro and in vivo

Many angiotensin-converting enzyme (ACE) inhibitors, identified by the suffix pril have secondary amines that can potentially react to form nitrosamines. Here we consider a structural assessment and metabolism data, coupled with comprehensive genotoxicity testing to evaluate this particular class of nitrosamines. These nitrosamines are concluded to be non-mutagenic and non-carcinogenic; therefore, they should be controlled according to ICH Q3B guidance. Furthermore, these results for N-nitroso ramipril and N-nitroso quinapril should be considered when evaluating the appropriate AI and control strategy for other structurally similar pril NDSRIs.

以“普利（pril）”为后缀的血管紧张素转换酶（ACE）抑制剂大多含有仲胺基团，此类基团可潜在发生反应生成亚硝胺。本研究结合结构表征、代谢数据与全面的遗传毒性试验，对该类特定亚硝胺开展评估。经评估，此类亚硝胺被证实为非致突变性、非致癌性物质，因此应依据ICH Q3B指导原则对其进行管控。此外，在评估其他结构相似的“普利”类NDSRIs的适宜AI与管控策略时，应参考N-亚硝胺基雷米普利与N-亚硝胺基喹那普利的相关研究结果。