液质联用技术在化学药杂质谱研究中的应用
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摘要
药品中杂质的存在影响着药品质量安全,杂质谱的研究对优化药品的合成工艺、处方工艺、包装及储藏条件具有重要指导意义。如何全面、合理、正确的确证及限量药品中存在的杂质是杂质谱研究的关键。而采用液质联用技术可以推导药品中杂质的结构,为制定科学合理的质量标准及药品生产提供依据与指导。本文探讨了液质联用技术在化学药杂质谱研究中的应用。
The presence of impurities in drugs affect the quality and safety of drugs,it is important guiding significance that the study of impurity profile can optimize the synthesis process of drugs,formulation technology,packaging and storage conditions. How to fully confirmed the correct and reasonable limited drug impurities is the key to study the impurity profile. The structure of pharmaceutical impurities can be derived by liquid chromatography-mass spectrometry( LC-MS),it provides basis and guidance in favour of developing scientific and rational quality standard and drugs-manufacturing. In this article,we discuss the application to study impurity profiling of chemical drugs by liquid chromatography-mass spectrometry technology.
The presence of impurities in drugs affect the quality and safety of drugs,it is important guiding significance that the study of impurity profile can optimize the synthesis process of drugs,formulation technology,packaging and storage conditions. How to fully confirmed the correct and reasonable limited drug impurities is the key to study the impurity profile. The structure of pharmaceutical impurities can be derived by liquid chromatography-mass spectrometry( LC-MS),it provides basis and guidance in favour of developing scientific and rational quality standard and drugs-manufacturing. In this article,we discuss the application to study impurity profiling of chemical drugs by liquid chromatography-mass spectrometry technology.
引文
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[12]蒋煜.化学药物制剂处方工艺的研究[J].中国新药杂志,2008,17(22):1990-1992.
[13]秦雯雯,王庆伟,赵波,等.HPLC-MS法测定药品含量的不确定评定[J].转化医学电子杂志,2017,4(11):90-92.
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[15]黄珊,李悦,朱红激.大环内酯类抗生素杂质谱研究进展[J].中国医药工业杂志,2015,46(3):299-305.
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[18]周长朋,王东武,张曼玉,等.高效液相色谱-四极杆/线性离子阱质谱仪测定盐酸决奈达隆中两种基因毒性杂质的痕量残留[J].分析测试学报,2016,35(9):1111-1115.
[19]杨昊,袁耀佐,赵恂,等.用HPLC-ESI-IT-MSn法研究庆大霉素C1a的杂质谱[J].药学与临床研究,2012,20(5):413-418.
[20]Zhu PX,Lu JX,Hong LY,et al.Characterization of an unknown impurity in doxofylline using LC-MS and NMR[J].J Pharm Biomed Anal,2017,140:31-37.
[21]Zhu PX,Lu JX,Wang ZJ,et al.Characterization of impurities in sodium cromoglycate drug substance and eye drops using LC-ESI-ion trap MS and LC-ESI-QTOF MS[J].J Pharm Biomed Anal,2017,145:537-548.
[22]Kumar N,Devineni SR,Gajjala PR,et al.Synthesis,isolation,identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC,LC/ESI-MS and NMR[J].J Pharm Anal,2017,7(6):394-400.
[23]Yang Y,Lian Y,Zhong P,et al.Characterization and quantitative analysis of related substances in Coenzyme A by HPLC and LC-MS/MS[J].J Pharm Biomed Anal,2018,150:220-232.
[24]戴冬艳,朱静毅,闻琍毓.液相色谱质谱联用技术在药物分析中的应用[J].天津药学,2012,24(3):50-53.
[2]侯玉荣,袁耀佐,张玫,等.应用LC-MS鉴定头孢呋辛酯的同分异构体[J].药学与临床研究,2017,25(2):91-94.
[3]闫存玉,赵毅民,乔善义,等.莫诺甙环口差向异构体的HPLC和ESI-TOF-MS分析[J].高等学校化学学报,2003,24(10):1784-1786.
[4]国家食品药品监督管理局.化学药物杂质研究的技术指导原则(2005年)[S].北京:中国医药科技出版社,2006:17.
[5]祝清芬,李涛,国明,等.药物杂质的毒理学评价要求及进展[J].中国新药杂志,2010,19(24):2271-2276.
[6]李真,龚培力,曹繁典.药物杂质及其对安全性的影响[J].中国临床药理学杂志,2001,17(6):451-453.
[7]胡昌勤.化学药品杂质控制的现状与展望[J].中国科学,2010,40(6):679-687.
[8]周莹,王晓霞.应用Qb D实验设计方案开发万古霉素杂质的色谱分离方法[A].中国药学会第四届药物检测质量管理学术研讨会[C].2017.
[9]魏农农.创新性化学药物杂质研究目的、思路与技术要求[J].中国新药杂志,2008,17(16):1461-1463.
[10]王永毅,冯锋,田连忠,等.半合成紫杉醇工艺杂质研究[J].中国现代应用药学,2014,31(2):154-158.
[11]Parramg MGDL,Rodriguez-loaiza P,Namur S.Using structural equation modeling(SEM)for the study of impurity profiles of drug substances[J].Quality Engineering,2006,18(2):225-235.
[12]蒋煜.化学药物制剂处方工艺的研究[J].中国新药杂志,2008,17(22):1990-1992.
[13]秦雯雯,王庆伟,赵波,等.HPLC-MS法测定药品含量的不确定评定[J].转化医学电子杂志,2017,4(11):90-92.
[14]陶林,田晓娟,佟利家.浅议药品杂质分析的方法验证[J].首都食品与医药,2013(24):5.
[15]黄珊,李悦,朱红激.大环内酯类抗生素杂质谱研究进展[J].中国医药工业杂志,2015,46(3):299-305.
[16]胡昌勤.药物杂质谱分析[M].北京:化学工业出版社,2015:3.
[17]王明娟,胡昌勤.采用串联质谱法建立大环内酯类抗生素杂质谱的思路[J].药学学报,2013,48(5):642-647.
[18]周长朋,王东武,张曼玉,等.高效液相色谱-四极杆/线性离子阱质谱仪测定盐酸决奈达隆中两种基因毒性杂质的痕量残留[J].分析测试学报,2016,35(9):1111-1115.
[19]杨昊,袁耀佐,赵恂,等.用HPLC-ESI-IT-MSn法研究庆大霉素C1a的杂质谱[J].药学与临床研究,2012,20(5):413-418.
[20]Zhu PX,Lu JX,Hong LY,et al.Characterization of an unknown impurity in doxofylline using LC-MS and NMR[J].J Pharm Biomed Anal,2017,140:31-37.
[21]Zhu PX,Lu JX,Wang ZJ,et al.Characterization of impurities in sodium cromoglycate drug substance and eye drops using LC-ESI-ion trap MS and LC-ESI-QTOF MS[J].J Pharm Biomed Anal,2017,145:537-548.
[22]Kumar N,Devineni SR,Gajjala PR,et al.Synthesis,isolation,identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC,LC/ESI-MS and NMR[J].J Pharm Anal,2017,7(6):394-400.
[23]Yang Y,Lian Y,Zhong P,et al.Characterization and quantitative analysis of related substances in Coenzyme A by HPLC and LC-MS/MS[J].J Pharm Biomed Anal,2018,150:220-232.
[24]戴冬艳,朱静毅,闻琍毓.液相色谱质谱联用技术在药物分析中的应用[J].天津药学,2012,24(3):50-53.