Article(id=1322906929084900034, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322887411688919265, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1629216000000, acceptedDateStr=2021-08-18, onlineDate=1793335190315, onlineDateStr=2026-10-30, pubDate=1636905600000, pubDateStr=2021-11-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793335190315, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793335190315, creator=13701087609, updateTime=1793335190315, updator=13701087609, issue=Issue{id=1322887411688919265, tenantId=1146029695717560320, journalId=1235980733773295621, year='2021', volume='30', issue='21', pageStart='1921', pageEnd='2016', issueExtLink='null', onlineDate='null', pubDate='1636905600000', pubDateStr='2021-11-15', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793330537006, creator='13701087609', updateTime=1793337443794, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322916380919608076, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322887411688919265, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322916380919608077, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322887411688919265, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1998, endPage=2002, ext={EN=ArticleExt(id=1322906930846507715, articleId=1322906929084900034, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Determination and risk analysis for potential N-nitrosamines in azithromycin injection, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective:

To identify the potential risk of N-nitrosamines in azithromycin and to establish corresponding method for confirmatory testing, providing reference for risk assessment by manufacturers.

Methods:

In conformity with the relevant industry guidance of FDA and EMA, risk identification and control limits for potential N-nitrosamines in azithromycin was conducted based on the structure and synthetic route, as well as degradation test. A liquid chromatography-mass spectrometry method was subsequently established and applied to the confirmatory testing of N-nitrosodimethylamine in azithromycin injection of 61 batches from 15 different manufacturers.

Results:

N-nitrosodimethylamine was probably introduced from starting material or generated as the degradation product of azithromycin. In all cases, N-nitrosodimethylamine were found below the limit of quantitation.

Conclusion:

The risk of potential N-nitrosamines in azithromycin injection was acceptable. This method proved sensitive, selective, accurate and suitable to the confirmatory testing and quality control of N-nitrosodimethylamine in azithromycin injection. The article also provided an example to the risk assessment and confirmatory testing of potential N-nitrosamines in chemically synthesized APIs and drug products.

, authors=Yang WU, Qi XU, Yan QIAN, Yi-wen HUANG, authorsList=Yang WU, Qi XU, Yan QIAN, Yi-wen HUANG, authorCompany=null, correspAuthors=Yi-wen HUANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322906931114943172, articleId=1322906929084900034, tenantId=1146029695717560320, journalId=1235980733773295621, language=CN, title=阿奇霉素注射剂中潜在N-亚硝胺的测定与风险分析, columnId=1236330556003242277, journalTitle=中国新药杂志, columnName=实验研究, runingTitle=null, highlight=null, articleAbstract=
目的:

识别阿奇霉素中潜在N-亚硝胺风险,并建立相应测定方法进行确认性检测,为生产企业开展风险评估提供借鉴。

方法:

按照美国FDA、欧洲EMA发布的相关指南,基于阿奇霉素结构特点与合成工艺,结合降解实验,对其中可能存在的N-亚硝胺风险进行识别,确定控制限度,并建立相应的HPLC-MS/MS法,对15个厂家的61批阿奇霉素注射剂中潜在N-亚硝基二甲胺(NDMA)含量进行确认性检测。

结果:

阿奇霉素有由原料直接引入或氧化降解生成NDMA的风险;实际收集的61批样品中NDMA含量均低于定量限。

结论:

市面上阿奇霉素注射剂中NDMA风险可控;建立的HPLC-MS/MS法灵敏度满足限度要求,专属性回收率精密度良好,可用于生产企业对阿奇霉素中NDMA风险评估的确认性检测与质量控制,也可为其他化学合成药品中潜在N-亚硝胺风险评估与测定提供借鉴。

, authors=吴杨, 许奇, 钱岩, 黄逸文, authorsList=吴杨, 许奇, 钱岩, 黄逸文, authorCompany=null, correspAuthors=黄逸文, authorNote=

吴杨,男,副主任药师,主要从事药品质量控制研究。E-mail:。

, correspAuthorsNote=
黄逸文,男,主管药师,主要从事药物合成工艺研究与质量研究。E-mail:。
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吴杨,男,副主任药师,主要从事药品质量控制研究。E-mail:。

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吴杨,男,副主任药师,主要从事药品质量控制研究。E-mail:。

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refs=[Reference(id=1322906933233066724, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1322906929084900034, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=null, journalName=null, refType=null, unstructuredReference=国家药监局药审中心. 国家药监局药审中心关于发布《化学药物中亚硝胺类杂质研究技术指导原则(试行)》的通告(2020年1号)[EB/OL]. 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阿奇霉素注射剂中潜在N-亚硝胺的测定与风险分析
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吴杨 , 许奇 , 钱岩 , 黄逸文
中国新药杂志 | 实验研究 2021,30(21): 1998-2002
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中国新药杂志 |实验研究 2021 , 30 (21) : 1998 -2002
阿奇霉素注射剂中潜在N-亚硝胺的测定与风险分析
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吴杨 , 许奇, 钱岩, 黄逸文
作者信息
  • 苏州市药品检验检测研究中心,苏州市药品不良反应监测中心,苏州 215000
通讯作者:
黄逸文,男,主管药师,主要从事药物合成工艺研究与质量研究。E-mail:。
作者简介:

吴杨,男,副主任药师,主要从事药品质量控制研究。E-mail:。

Determination and risk analysis for potential N-nitrosamines in azithromycin injection
Yang WU , Qi XU, Yan QIAN, Yi-wen HUANG
Affiliations
  • Suzhou Institute for Drug Control, Suzhou Centre of Adverse Drug Reaction Monitoring, Suzhou 215000, China
出版时间: 2021-11-15
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目的:

识别阿奇霉素中潜在N-亚硝胺风险,并建立相应测定方法进行确认性检测,为生产企业开展风险评估提供借鉴。

方法:

按照美国FDA、欧洲EMA发布的相关指南,基于阿奇霉素结构特点与合成工艺,结合降解实验,对其中可能存在的N-亚硝胺风险进行识别,确定控制限度,并建立相应的HPLC-MS/MS法,对15个厂家的61批阿奇霉素注射剂中潜在N-亚硝基二甲胺(NDMA)含量进行确认性检测。

结果:

阿奇霉素有由原料直接引入或氧化降解生成NDMA的风险;实际收集的61批样品中NDMA含量均低于定量限。

结论:

市面上阿奇霉素注射剂中NDMA风险可控;建立的HPLC-MS/MS法灵敏度满足限度要求,专属性回收率精密度良好,可用于生产企业对阿奇霉素中NDMA风险评估的确认性检测与质量控制,也可为其他化学合成药品中潜在N-亚硝胺风险评估与测定提供借鉴。

N-亚硝胺  /  阿奇霉素注射剂  /  HPLC-MS/MS  /  风险分析
Objective:

To identify the potential risk of N-nitrosamines in azithromycin and to establish corresponding method for confirmatory testing, providing reference for risk assessment by manufacturers.

Methods:

In conformity with the relevant industry guidance of FDA and EMA, risk identification and control limits for potential N-nitrosamines in azithromycin was conducted based on the structure and synthetic route, as well as degradation test. A liquid chromatography-mass spectrometry method was subsequently established and applied to the confirmatory testing of N-nitrosodimethylamine in azithromycin injection of 61 batches from 15 different manufacturers.

Results:

N-nitrosodimethylamine was probably introduced from starting material or generated as the degradation product of azithromycin. In all cases, N-nitrosodimethylamine were found below the limit of quantitation.

Conclusion:

The risk of potential N-nitrosamines in azithromycin injection was acceptable. This method proved sensitive, selective, accurate and suitable to the confirmatory testing and quality control of N-nitrosodimethylamine in azithromycin injection. The article also provided an example to the risk assessment and confirmatory testing of potential N-nitrosamines in chemically synthesized APIs and drug products.

N-nitrosamines  /  azithromycin injection  /  HPLC-MS/MS  /  risk analysis
吴杨, 许奇, 钱岩, 黄逸文. 阿奇霉素注射剂中潜在N-亚硝胺的测定与风险分析. 中国新药杂志, 2021 , 30 (21) : 1998 -2002 .
Yang WU, Qi XU, Yan QIAN, Yi-wen HUANG. Determination and risk analysis for potential N-nitrosamines in azithromycin injection[J]. Chinese Journal of New Drugs, 2021 , 30 (21) : 1998 -2002 .

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2021年第30卷第21期
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  • 首发时间:2026-10-30
  • 出版时间:2021-11-15
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    苏州市药品检验检测研究中心,苏州市药品不良反应监测中心,苏州 215000

通讯作者:

黄逸文,男,主管药师,主要从事药物合成工艺研究与质量研究。E-mail:。
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