GC-MS法检测利奈唑胺原料药中遗传毒性杂质S-环氧氯丙烷
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摘要
目的:建立测定利奈唑胺原料药中遗传毒性杂质S-环氧氯丙烷的方法。方法:采用气相色谱-质谱联用法。色谱柱为Agilent VF-624ms毛细管柱;柱温采用程序升温;进样口温度200℃;柱流量为1.0 ml·min~(-1);进样方式采用分流进样,分流比为5∶1;载气为高纯氦气;检测器为质谱检测器;离子化方式为EI;离子化电压为70 e V;离子源温度为210℃;传输线温度为240℃;溶剂延迟时间为4.5 min;检测方式为选择离子扫描模式(SIM);进样量为1μl。结果:空白溶剂与利奈唑胺均不干扰S-环氧氯丙烷的检测;在0.049 9~0.498 9μg·ml~(-1)浓度范围内S-环氧氯丙烷浓度与峰面积呈良好的线性关系(r=0.998 9);S-环氧氯丙烷平均回收率为97.66%,RSD为5.92%(n=9)。结论:该方法简便、准确、灵敏,可用于利奈唑胺原料药中遗传毒性杂质S-环氧氯丙烷的检测。
Objective: To establish a determination method for the genotoxicity impurity S-epichlorohydrin in linezolid raw material. Methods: A GC-MS method was conducted,the column was an Agilent VF-624 ms capillary column with programmed temperature,the inlet temperature was 200℃,the column flow was 1. 0 ml·min~(-1),split injection was used with the split ratio of 5∶ 1,the carrier gas was helium with high purity,a mass spectrometer detector was applied,the ionization mode was EI,the ionization voltage was 70 e V,the ion source temperature was 210℃,the transmission line temperature was 240℃,the delay time of solvent was 4. 5 min,the detection method was SIM,and the injection volume was 1. 0μl. Results: The blank solvent and linezolid showed no effects on the detection of Sepichlorohydrin. S-Epichlorohydrin showed good linearity within the range of 0. 049 9-0. 498 9 μg·ml~(-1)( r = 0. 998 9). The average recovery of S-epichlorohydrin was 97. 66% and the RSD was 5. 92%( n = 9). Conclusion: The method is simple,accurate and sensitive,and can be used for the determination of the genotoxicity impurities in linezolid raw material.
Objective: To establish a determination method for the genotoxicity impurity S-epichlorohydrin in linezolid raw material. Methods: A GC-MS method was conducted,the column was an Agilent VF-624 ms capillary column with programmed temperature,the inlet temperature was 200℃,the column flow was 1. 0 ml·min~(-1),split injection was used with the split ratio of 5∶ 1,the carrier gas was helium with high purity,a mass spectrometer detector was applied,the ionization mode was EI,the ionization voltage was 70 e V,the ion source temperature was 210℃,the transmission line temperature was 240℃,the delay time of solvent was 4. 5 min,the detection method was SIM,and the injection volume was 1. 0μl. Results: The blank solvent and linezolid showed no effects on the detection of Sepichlorohydrin. S-Epichlorohydrin showed good linearity within the range of 0. 049 9-0. 498 9 μg·ml~(-1)( r = 0. 998 9). The average recovery of S-epichlorohydrin was 97. 66% and the RSD was 5. 92%( n = 9). Conclusion: The method is simple,accurate and sensitive,and can be used for the determination of the genotoxicity impurities in linezolid raw material.
引文
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6 European Medicines Agency.Guideline on the Limits of Henotoxic Impurities[S].2006
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8赵丽,张瑞雨,师真,等.气相色谱法测定生活饮用水中环氧氯丙烷[J].安徽农业科学,2016,44(28):48-49
9吴正华,余胜兵,苏广宁,等.气相色谱-质谱联用法测定饮用水中的环氧氯丙烷[J].华南预防医学,2015,41(5):479-481
10周华,张蕴,金莞尔,等.吹扫捕集-气质联用技术测定饮用水中痕量环氧氯丙烷[J].中国预防医学杂志,2015,16(4):283-286
11 Vali SJ,Ganduri RJ,Sait SS.Estimation of epichorohydrin content in pharmaceutical drug substances by capillary gas chromatography with flame ionization detection[J].J Chem Pharm Res,2011,3(6):392-399
2 Clemett D,Markham A.Linezolid[J].Drugs,2000,59(4):815-827
3李桂杰,赵静国,张飞,等.新型抗菌药利奈唑胺合成的研究[J].化学与生物工程,2013,30(1):57-59
4马磊,马玉楠,陈震,等.遗传毒性杂质的警示结构[J].中国新药杂志,2014,23(18):2106-2111
5王萍,徐彩虹,陈仙,等.原料药中基因毒性杂质控制的研究进展[J].中国现代应用药学,2015,32(1):119-126
6 European Medicines Agency.Guideline on the Limits of Henotoxic Impurities[S].2006
7史继峰.EMEA《遗传毒性杂质限度指导原则》介绍[EB/OL].(2007-08-20)[2013-08-01]http://www.cde.org.cn/dzkw.do?method=large Page&id=2054
8赵丽,张瑞雨,师真,等.气相色谱法测定生活饮用水中环氧氯丙烷[J].安徽农业科学,2016,44(28):48-49
9吴正华,余胜兵,苏广宁,等.气相色谱-质谱联用法测定饮用水中的环氧氯丙烷[J].华南预防医学,2015,41(5):479-481
10周华,张蕴,金莞尔,等.吹扫捕集-气质联用技术测定饮用水中痕量环氧氯丙烷[J].中国预防医学杂志,2015,16(4):283-286
11 Vali SJ,Ganduri RJ,Sait SS.Estimation of epichorohydrin content in pharmaceutical drug substances by capillary gas chromatography with flame ionization detection[J].J Chem Pharm Res,2011,3(6):392-399