亚硝胺类药物相关杂质（NDSRI）与原料药（API）具有结构相似性（在化学结构中具有API或API片段），是每种原料药特有的杂质。NDSRI通常是由药物制剂中含有仲胺或叔胺的API（或API片段）在接触亚硝化剂（如制剂辅料中的残留亚硝酸盐）时形成。NDSRI通常缺乏致癌性和致突变性试验数据，因此无法根据该数据确定可接受摄入量限度。美国美国食品药品监督管理局（FDA）于2023年8月发布了“亚硝胺类药物相关杂质推荐可接受摄入量限度行业指导原则”，该指导原则重点介绍了如何利用亚硝胺类杂质的结构特点预测其致癌性，并根据致癌潜力类型确定该杂质可接受摄入量限度的方法。详细介绍FDA该指导原则的前言、背景，根据该指导原则提出了根据预测的致癌性分类确定可接受摄入量限度内容和对NDSRI推荐的可接受摄入量限度的实施的具体建议，期望能为我国亚硝胺类杂质可接受摄入量限度的研究和监管提供一定的参考。

Nitrosamine drug substance-related impurities (NDSRIs) share structural similarity to the API (having the API or API fragment in the chemical structure) and are therefore unique to each API. NDSRIs generally form in the drug product through nitrosation of APIs (or API fragments) that have secondary or tertiary amines when exposed to nitrosating agents such as residual nitrites in excipients used to formulate the drug product. NDSRIs often lack carcinogenicity and mutagenicity study data from which an acceptable intake limit can be determined. In August 2023, the FDA issued the " Recommended Acceptable Intake Limits for Nitrosamine Drug Substance Related Impurities Guidance for Industry", which focused on how to use the structural characteristics of nitrosamine impurities to predict their carcinogenicity, and determine the acceptable intake limits of the impurities according to carcinogenic potency category.This paper introduces the content of FDA's guideline in detail, hoping to provide some reference for the research and supervision of acceptable intake limits of nitrosamine impurities in China.

R979.1