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  2 9 1 2 5 3 2 位浏览者
您当前的位置:首页 >> 正文

基因毒性杂质分析方法和前处理技术的研究进展

Advances in analytical methods and pre-treatment techniques for genotoxic impurities

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (10):1668-1676
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

基因毒性杂质对人们的用药安全造成了严重威胁。由于性质活泼、稳定性差,基因毒性杂质的痕量分析极具挑战性。本文系统地介绍9种基因毒性杂质(烷基卤化物、双烷基硫酸酯、环氧化合物、肼类化合物、四甲基哌啶氧化物、芳香胺、硼酸、磺酸酯和乙酰胺)的分析方法(包括GC、LC、GC-MS和LC-MS法等)及其前处理技术(包括顶空分析法、固相萃取法和衍生化法等),为更好地选择和建立基因毒性杂质的检测方法提供重要参考。

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

Genotoxic impurities pose a serious threat to people's safety of medication. Trace-level analysis of genotoxic impurities is challenging due to the active property and poor stability. This article systematically introduces the analytical methods including GC, LC, GC-MS and LC-MS, and the pre-treatment techniques containing headspace, solid-phase extraction and derivatization for the nine kinds of genotoxic impurities:alkyl halides, dialkyl sulfates, epoxides, hydrazines, TEMPO, aromatic amines, boronic acids, sulfonate esters and acetamide. It will be beneficial for the better selection and establishment of analysis methods for genotoxic impurities.

-----参考文献:---------------------------------------------------------------------------------------
[1] REDDY AVB,JAAFAR J,UMAR K,et al.Identification,control strategies,and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals:a comprehensive review[J].J Sep Sci,2015,38(5):764
[2] LIU DQ,SUN MJ,KORD AS.Recent advances in trace analysis of pharmaceutical genotoxic impurities[J].J Pharm Biomed,2010,51(5):999
[3] ICH M7(R1).Assessment and Control of DNA Reactive (Mutagenic)Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk[EB/OL].[2017-11-11].http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M7/M7_R1_Addendum_Step_4_2017_0331.pdf
[4] FDA Guidance for Industry Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals.[EB/OL].[2017-11-11].https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm074925.pdf
[5] EMEA.Guideline on the Limit of Genotoxic Impurities[EB/OL].[2017-11-11].http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002903.pdf
[6] BENIGNI R,BOSSA C.Structural alerts of mutagens and carcinogens[J].Curr Comput Aid Drug,2006,2(2):169
[7] Development of Structure Alerts for the In Vivo Micronucleus Assay in Rodents[DB/OL].[2017-11-11].https://eurl-ecvam.jrc.ec.europa.eu/laboratories-research/predictive_toxicology/doc/EUR_23844_EN.pdf
[8] DOBO KL,GREENE N,CYR MO,et al.The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development[J].Regul Toxicol Pharm,2006,44(3):282
[9] MCGOVERN T,JACOBSON-KRAM D.Regulation of genotoxic and carcinogenic impurities in drug substances and products[J].Trac-Trend Anal Chem,2006,25(8):790
[10] EMEA.European Medicines Agency announces recall of Viracept[EB/OL].[2017-11-11].http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500014207.pdf
[11] SZEKELY G,DE SOUSA MCA,GIL M,et al.Genotoxic impurities in pharmaceutical manufacturing:sources,regulations,and mitigation[J].Chem Rev,2015,115(16):8182
[12] ELDER DP,LIPCZYNSKI AM,TEASDALE A.Control and analysis of alkyl and benzyl halides and other related reactive organohalides as potential genotoxic impurities in active pharmaceutical ingredients(APIs)[J].J Pharm Biomed,2008,48(3):497
[13] HO TD,YEHL PM,CHETWYN NP,et al.Determination of trace level genotoxic impurities in small molecule drug substances using conventional headspace gas chromatography with contemporary ionic liquid diluents and electron capture detection[J].J Chromatogr A,2014,1361:217
[14] FROST RP,HUSSAIN MS,RAGHANI AR.Determination of pharmaceutical process impurities by solid phase microextraction gas chromatography[J].J Sep Sci,2003,26(12-13):1097
[15] HO TD,JOSHI MD,SILVER MA,et al.Selective extraction of genotoxic impurities and structurally alerting compounds using polymeric ionic liquid sorbent coatings in solid-phase microextraction:alkyl halides and aromatics[J].J Chromatogr A,2012,1240:29
[16] BAI L,SUN M,AN J,et al.Enhancing the detection sensitivity of trace analysis of pharmaceutical genotoxic impurities by chemical derivatization and coordination ion spray-mass spectrometry[J].J Chromatogr A,2010,1217(3):302
[17] van WIJK AM,NIEDERLANDER HAG,SIEBUM AHG,et al.A new derivatization reagent for LC-MS/MS screening of potential genotoxic alkylation compounds[J].J Pharm Biomed,2013,74:133
[18] HOOGERHEIDE JG,SCOTT RA.Use of 2-mercaptopyridine for the determination of alkylating agents in complex matrices:application to dimethyl sulfate[J].Talanta,2005,65(2):453
[19] GRINBERG N,ALBU F,FANDRICK K,et al.Assay at low ppm level of dimethyl sulfate in starting materials for API synthesis using derivatization in ionic liquid media and LC-MS[J].J Pharm Biomed,2013,75:1
[20] LEE CR,GUIVARCH F,VAN DAU CN,et al.Determination of polar alkylating agents as thiocyanate/isothiocyanate derivatives by reaction headspace gas chromatography[J].Analyst,2003,128(7):857
[21] AN JG,SUN MJ,BAI L,et al.A practical derivatization LC/MS approach for determination of trace level alkyl sulfonates and dialkyl sulfates genotoxic impurities in drug substances[J].J Pharm Biomed,2008,48(3):1006
[22] ALZAGA R,RYAN RW,TAYLOR-WORTH K,et al.A generic approach for the determination of residues of alkylating agents in active pharmaceutical ingredients by in situ derivatization-headspace-gas chromatography-mass spectrometry[J].J Pharm Biomed,2007,45(3):472
[23] BRINKER AM,RASKIN I.Determination of triptolide in root extracts of Tripterygium wilfordii by solid-phase extraction and reverse-phase high-performance liquid chromatography[J].J Chromatogr A,2005,1070(1-2):65
[24] KURSINSZKI L,HANK H,LASZLO I,et al.Simultaneous analysis of hyoscyamine,scopolamine,6 beta-hydroxyhyoscyamine and apoatropine in solanaceous hairy roots by reversed-phase high-performance liquid chromatography[J].J Chromatogr A,2005,1091(1-2):32
[25] TAPPIN MRR,NAKAMURA MJ,SIANI AC,et al.Development of an HPLC method for the determination of tetranortriterpenoids in Carapa guianensis seed oil by experimental design[J].J Pharm Biomed,2008,48(4):1090
[26] WU L,LIU DQ,VOGT FG,et al.Gas-phase derivatization via the Meerwein reaction for selective and sensitive LC-MS analysis of epoxides in active pharmaceutical ingredients[J].J Pharm Biomed Anal,2011,56(5):1106
[27] BRUZZONITI MC,ANDRENSEK S,NOVIC M,et al.Determination of epichlorohydrin by sulfite derivatization and ion chromatography:characterization of the sulfite derivatives by ion chromatography-mass spectrometry[J].J Chromatogr A,2004,1034(1-2):243
[28] SETOH M,ISHⅡ N,KONO M,et al.Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52[J].J Med Chem,2014,57(12):5226
[29] LUKIN K,HSU MC,FERNANDO D,et al.New practical synthesis of indazoles via condensation of o-fluorobenzaldehydes and their O-methyloximes with hydrazine[J].J Org Chem,2006,71(21):8166
[30] NAKHAI A,BERGMAN J.Synthesis of hydrogenated indazole derivatives starting with alpha,beta-unsaturated ketones and hydrazine derivatives[J].Tetrahedron,2009,65(11):2298
[31] KOVACIC P,JACINTHO JD.Mechanisms of carcinogenesis:focus on oxidative stress and electron transfer[J].Curr Med Chem,2001,8(7):773
[32] FORTIN DT,CHEN R.Developing a trace level GC-MS method for detecting methylhydrazine in an experimental drug substance[J].J Chromatogr Sci,2010,48(4):299
[33] WANG J,YANG S,ZHANG K.A simple and sensitive method to analyze genotoxic impurity hydrazine in pharmaceutical materials[J].J Pharm Biomed,2016,126:141
[34] CUI L,JIANG KN,LIU DQ,et al.Simultaneous quantitation of trace level hydrazine and acetohydrazide in pharmaceuticals by benzaldehyde derivatization with sample ‘matrix matching’ followed by liquid chromatography-mass spectrometry[J].J Chromatogr A,2016,1462:73
[35] SUN MJ,BAI L,LIU DQ.A generic approach for the determination of trace hydrazine in drug substances using in situ derivatization-headspace GC-MS[J].J Pharm Biomed,2009,49(2):529
[36] DAMIANI E,GRECI L,HRELIA P.Cyto-and genotoxic effects of novel aromatic nitroxide radicals in vitro[J].Free Radic Biol Med,2000,28(3):330
[37] STROHMEYER HE,SLUGGETT GW.Determination and control of TEMPO,a potentially genotoxic free radical reagent used in the synthesis of filibuvir[J].J Pharm Biomed,2012,62:216
[38] PENNINGTON J,COHEN RD,TIAN Y,et al.Development of an LC-MS method for ultra trace-level determination of 2,2,6,6-tetramethylpiperidine-1-oxl (TEMPO),a potential genotoxic impurity within active pharmaceutical ingredients[J].J Pharm Biomed,2015,114:488
[39] SNODIN DJ.Genotoxic impurities:from structural alerts to qualification[J].Org Process Res Dev,2010,14(4):960
[40] AZNAR M,CANELLAS E,NERIN C.Quantitative determination of 22 primary aromatic amines by cation-exchange solid-phase extraction and liquid chromatography-mass spectrometry[J].J Chromatogr A,2009,1216(27):5176
[41] JURADO-SANCHEZ B,BALLESTEROS E,GALLEGO M.Comparison of several solid-phase extraction sorbents for continuous determination of amines in water by gas chromatography-mass spectrometry[J].Talanta,2009,79(3):613
[42] HUANG MJ,TAI C,ZHOU QF,et al.Preparation of polyaniline coating on a stainless-steel wire using electroplating and its application to the determination of six aromatic amines using headspace solid-phase microextraction[J].J Chromatogr A,2004,1048(2):257
[43] LIU XY,JIA YS,ZHANG HX,et al.Highly sensitive analysis of substituted aniline compounds in water samples by using oxidized multiwalled carbon nanotubes as an in-tube solid-phase microextraction medium[J].J Chromatogr A,2008,1212(1-2):10
[44] BREDE C,SKJEVRAK I,HERIKSTAD H.Determination of primary aromatic amines in water food simulant using solid-phase analytical derivatization followed by gas chromatography coupled with mass spectrometry[J].J Chromatogr A,2003,983(1-2):35
[45] ZHAO X,SUO Y.Analysis of primary aromatic amines using precolumn derivatization by HPLC fluorescence detection and online MS identification[J].J Sep Sci,2008,31(4):646
[46] O'DONOVAN MR,MEE CD,FENNER S,et al.Boronic acids-A novel class of bacterial mutagen[J].Mutat Res-Gen Tox En,2011,724(1-2):1
[47] GALLOWAY SM,REDDY MV,MCGETTIGAN K,et al.Potentially mutagenic impurities:analysis of structural classes and carcinogenic potencies of chemical intermediates in pharmaceutical syntheses supports alternative methods to the default TTC for calculating safe levels of impurities[J].Regul Toxicol Pharm,2013,66(3):326
[48] HANSEN MM,JOLLY RA,LINDER RJ.Boronic acids and derivatives-probing the structure-activity relationships for mutagenicity[J].Org Process Res Dev,2015,19(11):1507
[49] PATEL I,VENKATRAMANI CJ,STUMPF A,et al.Trace analysis of potentially mutagenic boronic acids and esters in drug substance by ICP-MS[J].Org Process Res Dev,2017,21(2):182
[50] HAKEN JK,ABRAHAM F.Gas-chromatography of homologous estersⅩⅩⅩⅣ.Alkyl borate and boronate esters[J].J Chromatogr,1991,550(1-2):155
[51] NAYLOR S,BENSON LM,TOMLINSON AJ.Application of capillary electrophoresis and related techniques to drug metabolism studies[J].J Chromatogr A,1996,735(1-2):415
[52] FORST MB,WARNER AM.Development and validation of non-aqueous capillary electrophoresis methods to analyze boronic esters and acids[J].J Pharm Biomed,2012,64-65:49
[53] WOLLEIN U,SCHRAMEK N.Simultaneous determination of alkyl mesilates and alkyl besilates in finished drug products by direct injection GC/MS[J].Eur J Pharm Sci,2012,45(1-2):201
[54] European Directorate for Quality and Medicines & Health Care(EDQM).Methyl,ethyl and isopropyl methanesulfonate in methanesulfonic acid[EB/OL].[2017-11-11].https://www.edqm.eu/sites/default/files/publication_calendar_for_the_9th_edition_pheur.pdf
[55] COLON I,RICHOLL SM.Determination of methyl and ethyl esters of methanesulfonic,benzenesulfonic and p-toluenesulfonic acids in active pharmaceutical ingredients by solid-phase microextraction (SPME)coupled to GC/SIM-MS[J].J Pharm Biomed,2005,39(3-4):477
[56] GARCIA A,RUPEREZ FJ,CEPPA F,et al.Development of chromatographic methods for the determination of genotoxic impurities in cloperastine fendizoate[J].J Pharm Biomed,2012,61:230
[57] European Directorate for Quality and Medicines & Health Care (EDQM).Methyl,ethyl and isopropyl methanesulfonate in active substances[EB/OL].[2017-11-11].https://www.edqm.eu/sites/default/files/publication_calendar_for_the_9th_edition_pheur.pdf
[58] ZHOU J,XU J,ZHENG XY,et al.Determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid by derivatization followed by high-performance liquid chromatography with ultraviolet detection[J].J Sep Sci,2017,40(17):3414
[59] SCHULE A,ATES C,PALACIO M,et al.Monitoring and control of genotoxic impurity acetamide in the synthesis of zaurategrast sulfate[J].Org Process Res Dev,2010,14(4):1008
[60] ELIAS G,MATTSON ED,LITTLE JE.An HPLC method for the quantification of butyramide and acetamide at ppb levels in hydrogeothermal waters[J].Anal Methods-UK,2012,4(2):530
[61] CHO YH,SHIN HS.Determination of trace levels of acetamide,propanamide,and butyramide in surface and drinking water using gas chromatography-mass spectrometry after derivatization with 9-xanthydrol[J].Anal Chim Acta,2013,787:111

欢迎阅读《药物分析杂志》!您是该文第 152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; 技术支持:010-60213898

电子邮件:ywfx@nicpbp.org.cn