HPLC法测定利奈唑胺中硝基苯类潜在遗传毒性杂质B的含量
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摘要
目的:建立高效液相色谱法测定利奈唑胺中硝基苯类潜在遗传毒性杂质B的含量。方法:以YMC ODSAM C_(18)(4.6 mm×150 mm,5μm)为色谱柱,以0.1%三氟乙酸溶液-0.1%三氟乙酸乙腈溶液(62∶38)为流动相,流速为1.0 m L·min~(-1),检测波长为368 nm,柱温为30℃。结果:杂质B在15~60 ng·m L~(-1)范围内,线性关系良好(R=0.9979);精密度和溶液稳定性均符合要求;高、中、低3种浓度的平均回收率分别为97.9%、98.2%和97.5%。结论:本方法专属性好,灵敏度高,精密度、准确度好,可用于利奈唑胺原料中硝基苯类潜在遗传毒性杂质的测定。
Objective: To establish a high performance liquid chromatography( HPLC) method for the determination of potential nitrobenzene genotoxic impurity B in Linezolid. Methods: The test was performed on YMC ODSAM C_(18) column( 4. 6 mm × 150 mm,5 μm) with 0. 1% TFA-0. 1% TFA/ACN( 62∶ 38) as the mobile phase. The flow rate was set as 1. 0 m L·min~(-1),the detection wavelength as 368 nm,and the column temperature as 30 ℃.Results: The linear range of calibration curve fell into 15-60 ng·m L~(-1)( r = 0. 9979). The precision and solution stability met the requirements. The average recoveries of three concentrations( high,middle,low) were 97. 9%,98. 2%,97. 5% respectively. Conclusion: The method has the good specificity,sensitivity,accuracy and precision. It can be used for determination of potential nitrobenzene genotoxic impurities in Linezolid.
Objective: To establish a high performance liquid chromatography( HPLC) method for the determination of potential nitrobenzene genotoxic impurity B in Linezolid. Methods: The test was performed on YMC ODSAM C_(18) column( 4. 6 mm × 150 mm,5 μm) with 0. 1% TFA-0. 1% TFA/ACN( 62∶ 38) as the mobile phase. The flow rate was set as 1. 0 m L·min~(-1),the detection wavelength as 368 nm,and the column temperature as 30 ℃.Results: The linear range of calibration curve fell into 15-60 ng·m L~(-1)( r = 0. 9979). The precision and solution stability met the requirements. The average recoveries of three concentrations( high,middle,low) were 97. 9%,98. 2%,97. 5% respectively. Conclusion: The method has the good specificity,sensitivity,accuracy and precision. It can be used for determination of potential nitrobenzene genotoxic impurities in Linezolid.
引文
[1]吴继禹,王志强,胡卢峰.利奈唑胺注射液含量测定的高效液相色谱法和紫外光度法的比较[J].中国卫生检验杂志,2011,21(10):2406WU JY,WANG ZQ,HU LF.Comparative study on the determination of Linezolid Injection by HPLC and UV spectrophotometry[J].Chin J Health Lab Technol,2011,21(10):2406
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[7]European Medicines Agency.Guideline on the Limits of Genotoxic Impurities[S].2006
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[9]利奈唑胺注射液进口注册标准[S].JX20120105The import registration specification of Linezolid injection[S].JX20120105
[2]黄志雄,桑志培,曹海彦,等.利奈唑胺注射液中主要降解产物的合成[J].有机化学,2014,34:989HUANG ZX,SANG ZP,CAO HY,et al.Synthesis of major degradation products of the injection of linezolid[J].Chin J Org Chem,2014,34:989
[3]黄成坷,周伶俐,吴伟明,等.HPLC测定利奈唑胺注射液中利奈唑胺的含量及其有关物质[J].中国现代应用药学,2012,29(7):655HUANG CK,ZHOU LL,WU WM,et al.Determination of linezolid content and related substances in linezolid injection by HPLC[J].Chin J Mod Appl Pharm,2012,29(7):655
[4]ELDER DP,TEASDALE A,LIPCZYNSKI AM.Control and analysis of alkyl and aryl sulfonic acids in novel active pharmaceutical ingredients(APIs)[J].J Pharm Biomed Anal,2008,46(1):1
[5]刘晓丹,陆峰,何伍.浅析遗传毒性杂质在医药工业中的来源与控制[J].药学服务与研究,2017,17(3):235LIU XD,LU F,HE W.Superficial analysis of sources and control of genotoxic impurities in pharmaceutical manufacturing[J].Pharm Care Res,2017,17(3):235
[6]马磊,马玉楠,陈震,等.遗传毒性杂质的警示结构.中国新药杂志,2014,23(18):2106MA L,MA YN,CHEN Z,et al.Structural alerts of genotoxic impurities[J].Chin J New Drug,2014,23(18:):2106
[7]European Medicines Agency.Guideline on the Limits of Genotoxic Impurities[S].2006
[8]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=2054SHI JF.European Medicines Agency:Guideline on the Limits of Genotoxic Impurities[EB/OL].(2007-08-20)[2013-08-01].http://www.cde.org.cn/dzkw.do?method=large Page&id=2054
[9]利奈唑胺注射液进口注册标准[S].JX20120105The import registration specification of Linezolid injection[S].JX20120105