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HPLC-MS/MS法测定依卡倍特钠原料药中潜在遗传毒性杂质 预览

Determination of potential genotoxic impurity in ecabet sodium active pharmaceutical ingredient by HPLC-MS/MS
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摘要 为了定量测定依卡倍特钠中潜在遗传毒性杂质依卡倍特磺酸乙酯(杂质Ⅰ),参考文献方法合成依卡倍特磺酸乙酯。采用高分辨质谱、结合二级质谱与核磁共振确定其相对分子质量及化学结构。采用Thermo C18色谱柱,以5 mmol/L乙酸铵溶液(甲酸调p H至3.0)为流动相A;乙腈为流动相B,按照梯度:0 min 50%B,4 min 50%B,12 min 80%B,16 min 80%B,16.1 min 50%B,20 min 50%B进行洗脱,柱温40℃;采用电喷雾负离子化-MS/MS选择反应监测。杂质Ⅰ的线性质量浓度范围为4-150 ng/m L,且线性关系良好(r=0.999);最低定量限为4 ng/m L;杂质Ⅰ的进样精密度、重复性和加标回收率良好,耐用性良好。方法操作简便,灵敏度高,可用于依卡倍特钠原料药中潜在遗传毒性杂质依卡倍特磺酸乙酯的含量测定。 To develop a sensitive analytical method for the determination of the genotoxic impurity mono ethyl ester of ecabet( Imp-I),an HPLC-MS/MS technique was employed. Imp-I was synthesized according to the previous literatures. MS/MS and NMR were used to confirm the structure of Imp-I. A Thermo C18 column was used for chromatographic separations. The mobile phase consisting of A: 5 mmol/L ammonium acetate( p H adjusted to 3. 0 with formic acid) and B: acetonitrile,with a gradient program: 0 min 50% B,4 min 50% B,12 min 80% B,16 min80% B,16. 1 min 50% B and 20 min 50% B. The column was maintained at 40 ℃ throughout the analysis. All measurements were carried out with the mass spectrometer operated under the negative ESI mode. The selective reaction monitor( SRM) transition was used. Good linearity was obtained for Imp-I over the concentration range of4-150 ng/m L with the coefficient of determination( r) of 0. 999. And the LOQ was 4 ng/m L. A rapid and sensitive HPLC-ESI-MS/MS method was developed for quantitative analysis of Imp-I in ecabet sodium APIs. This method can be of used for quality assurance of ecabet sodium in bulk commercial drugs.
作者 丁希颖 吉小龙 李博 毛白杨 严方 狄斌 DING Xiying 1,2 ,JI Xiaolong 3,LI Bo 1,2 ,MAO Baiyang 4,YAN Fang 1,2 ,DI Bin 1,2(1 Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University,Nanjing 210009; 2 Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009; 3 Department of Synthesis,Yabang Pharmaceutical Research Institute ,Changzhou 213161; 4 Yabang Pharmaceutical Co.,Ltd.,Changzhou 213161,China)
出处 《中国药科大学学报》 CSCD 北大核心 2018年第3期317-321,共5页 Journal of China Pharmaceutical University
关键词 依卡倍特钠 遗传毒性杂质 液相色谱-串联质谱 ecabet sodium genotoxic impurities HPLC-MS/MS
作者简介 通信作者Tel:025—83271269E-mail:cpuyanfang@hotmail.com;通信作者Tel:025-83271269E-mail:dibin@cpu.edu.cn
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  • 1王彦.盐酸阿扎司琼有机溶剂残留量测定[J].药物分析杂志,2004,24(3):293-295. 被引量:3
  • 2ZHU H, YUAN Y Q, SUN Q L, et al. Assignment of Chemical Shit~ of Ecabet Sodium [J]. Fine Chem Intermed , 2008, 38(5): 65-67. 被引量:1
  • 3WANG X D, LI C H. Clinical Efficacy of Ecabet Sodium and Famotidine in Treatment of Gastric Ulcer [J]. Med J Chin PAPF, 2007, 18(2): 118-120. 被引量:1
  • 4LIU X L. Clinical Efficacy of Ecabet Sodium in Treatment of Gastric Ulcer [J]. Chin J Med Guide, 2009, 11(6): 967-968. 被引量:1
  • 5ITO Y, ONODA Y, NAKAMURA S, et al. Effects of the new anti-ulcer drug ecabet sodium (TA-2711) on pepsin activity 1I: Interaction with substrate protein [J]. Jpn J Pharmacol, 1993, 62(2): 175-181. 被引量:1
  • 6SHIBATA K, ITO Y, HONGO A, et al. Bactericidal activity of a new antiulcer agent, ecabet sodium against helicobacter pylori under acidic conditions [J]. Antimicrob Agents Chemother, 1995, 39(6): 1295-1299. 被引量:1
  • 7ONODA Y, TAKIDO M, MAGARIBUCHI T, et al. Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric mucosal lesions induced by necrotizing agents and gastric mucosal defensive factors in rats [J]. Jpn J Pharmacol, 1990,52(4): 631-638. 被引量:1
  • 8LI Y F, ZHU L, TAO L H, et al. HPLC determination of contents and related substances of synthetic thymosin a1 [J]. Chin J Mod Appl Pharm , 2010, 27(3): 265-268. 被引量:1
  • 9GAO Z Y, ZHENG J, LI Y L, et al. Determination of crude drug di-phenyl-di-(2,4-difluobenzohydroxamato) tin and its related substances by HPLC [J]. Chin J Mod Appl Pharm, 2010, 27(12): 1119-1121. 被引量:1
  • 10ICH Q3A (R2), Impurities in New Drug Substances[ EB/OL]. (2006 - 10-25). [2014 -03 -31]. http://www, ich. org/ LOB/media/MEDIA422. pdf. 被引量:1

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