关闭
 
读者在线:用户名 密码
首页 期刊简介 投稿须知 期刊目录 专家风采 编委会 特邀顾问 联系我们 移动出版
  1. 1
  2. 2
  3. 3
  4. 4
  5. 5



刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

访问统计
您是第  4 9 9 2 3 4 0 位浏览者
您当前的位置:首页 >> 正文

LC-Q-TOF-MS法测定氯沙坦钾及其复方制剂中痕量杂质N-亚硝基-N-甲基-4-氨基丁酸

Determination of trace impurity NMBA in potassium losartan and its compound preparations by LC-Q-TOF-MS

分类号:R917
出版年·卷·期(页码):2019,39 (11):2047-2050
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:采用高效液相色谱-四极杆飞行时间质谱(LC-Q-TOF-MS)建立氯沙坦钾及其复方制剂中基因毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)的测定方法。方法:采用Agilent ZORBAX SB-C18色谱柱(2.1 mm×50 mm,1.8 μm)进行分离,流动相为0.1%甲酸水溶液-乙腈,梯度洗脱,流速0.3 mL·min-1;质谱采用电喷雾离子源,正离子模式下选择[M+H]+ m/z 147.076 4对NMBA进行测定。结果:NMBA在5~100 ng·mL-1浓度范围内线性良好,相关系数为0.995 6。定量下限(LOQ)为2.1 ng·mL-1,精密度试验和重复性试验RSD均小于10.0%。3批药品中均未检出NMBA。结论:本方法可用于氯沙坦钾及其复方制剂中NMBA的测定。

-----英文摘要:---------------------------------------------------------------------------------------

Objective: To determine the genotoxic impurity N-nitroso-N-methyl-4-amimobutyric acid (NMBA) in losartan potassium and its compound preparation by high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS). Methods: The separation was carried out on an Agilent ZORBAX SB-C18 column with the mobile phase consisting of 0.1% formic acid-water solution and acetonitrile. The flow rate was 0.3 mL·min-1 with gradient elution. Electronic spray ion (ESI) in positive ionization mode was performed and[M+H]+ m/z 147.0764 was extracted for the determination. Results: The calibration curve of NMBA was in good linearity with a correlation coefficient of 0.995 6 in the range of 5~100 ng·mL-1. The limit of quantification (LOQ) of NMBA was 2.1 ng·mL-1, and RSDs of both precision and repeatability tests were less than 10.0%. NMBA was not detected in the three batches of samples. Conclusion: The method can be used to determine NMBA in potassium losartan and its compound preparations.

-----参考文献:---------------------------------------------------------------------------------------

[1] 蔡鹏俊,李悦.几种沙坦类药物的杂志谱研究现状[J].药物分析杂志,2016,36(3):377 CAI PJ,LI Y.Research progress of sartans'impurity profile[J].Chin J Pharm Anal,2016,36(3):377
[2] 郭拥政,孙晓群,陈程,等.HPLC法测定缬沙坦中的遗传毒性杂志[J].中国药品标准,2016,17(5):337 GUO YZ,SUN XQ,CHEN C,et al.HPLC determination of genotoxic impurities in Valsartan[J].Drug Stand China,2016,17(5):337
[3] FDA.FDA provides update on its ongoing investigation into ARB drug products;reports on finding of a new nitrosamine impurity in certain lots of losartan and product recall[EB/OL].[2019-3-1] https://www.fda.gov/news-events/press-announcements/fda-provides-update-its-ongoing-investigation-arb-drug-products-reports-finding-new-nitrosamine
[4] FDA.FDA Updates and Press Announcements on Angiotensin Ⅱ Receptor Blocker (ARB) Recalls (Valsartan,Losartan,and Irbesartan)[EB/OL].[2019-6-12] https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan
[5] 钱建钦, 张云峰, 王建, 等.UHPLC-MS法测定2种硫酸氢氯吡格雷晶型中的基因毒性杂志对甲苯磺酸甲酯[J].药物分析杂志,2017,37(11):1994 QIAN JQ,ZHANG YF,WANG J,et al.Determination of genotoxic impurity methyl p-toluenesulfonate in two kinds of crystal forms of clopidogrel hydrogen sulfate[J].Chin J Pharm Anal, 2017,37(11):1994
[6] 张霁, 张英俊, 聂飚.药物研发中基因毒性杂志的控制策略与方法探索进展[J].中国医药工业杂志, 2018,49(9):1203 ZHANG J,ZHANG YJ,NIE B.Advances in control strategies and methods for genotoxic impurities in drug research and development[J].Chin J Pharm,2018,49(9):1203
[7] SNODIN DJ.Genotoxic impurities:from structural alerts to qualification[J].Org Process Res Dev,2010,14(4):960
[8] 谢含仪, 林云良, 张瑞凌, 等.基因毒性杂志分析方法和前处理技术的研究进展[J].药物分析杂志, 2018,38(10):1668 XIE HY,LIN YL,ZHANG RL,et al.Advances in analytical methods and pre-treatment techniques for genotoxic impurities[J].Chin J Pharm Anal, 2018,38(10):1668
[9] FDA.Development and validation of a Rapid Fire-MS/MS method for screening of nitrosamine carcinogen impurities N-nitrosodimethylamine (NDMA),N-Nitrosodiethylamine (NDEA),N-nitrosoethylisopropylamine (NEIPA),N-nitrosodiisopropylamine (NDIPA),N-nitrosodibutylamine (NDBA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA) in ARB drugs[EB/OL].[2019-06-02].https://www.fda.gov/media/125477/download
[10] FDA.Liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for the determination of six nitrosamine impurities in ARB drugs[EB/OL].[2019-06-02].https://www.fda.gov/media/125478/download

欢迎阅读《药物分析杂志》!您是该文第 455位读者!

药物分析杂志 © 2009
地址:北京天坛西里2号 邮政编码:100050; 电子邮件:ywfx@nicpbp.org.cn

本系统由北京博思汇文数字科技有限公司设计开发 技术服务电话:400-921-9838