亞硝胺類藥物相關(guān)雜質(zhì)（NDSRI）與原料藥（API）具有結(jié)構(gòu)相似性（在化學(xué)結(jié)構(gòu)中具有API或API片段），是每種原料藥特有的雜質(zhì)。NDSRI通常是由藥物制劑中含有仲胺或叔胺的API（或API片段）在接觸亞硝化劑（如制劑輔料中的殘留亞硝酸鹽）時(shí)形成。NDSRI通常缺乏致癌性和致突變性試驗(yàn)數(shù)據(jù)，因此無(wú)法根據(jù)該數(shù)據(jù)確定可接受攝入量限度。美國(guó)美國(guó)食品藥品監(jiān)督管理局（FDA）于2023年8月發(fā)布了“亞硝胺類藥物相關(guān)雜質(zhì)推薦可接受攝入量限度行業(yè)指導(dǎo)原則”，該指導(dǎo)原則重點(diǎn)介紹了如何利用亞硝胺類雜質(zhì)的結(jié)構(gòu)特點(diǎn)預(yù)測(cè)其致癌性，并根據(jù)致癌潛力類型確定該雜質(zhì)可接受攝入量限度的方法。詳細(xì)介紹FDA該指導(dǎo)原則的前言、背景，根據(jù)該指導(dǎo)原則提出了根據(jù)預(yù)測(cè)的致癌性分類確定可接受攝入量限度內(nèi)容和對(duì)NDSRI推薦的可接受攝入量限度的實(shí)施的具體建議，期望能為我國(guó)亞硝胺類雜質(zhì)可接受攝入量限度的研究和監(jiān)管提供一定的參考。

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