• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
RUAN Xiaoling, ZHENG Xiangyuan, XU Jie, DING Li, ZHENG Feng. Advances in analytical techniques for the determination of genotoxic impurities in pharmaceuticals[J]. Journal of China Pharmaceutical University, 2016, 47(3): 267-274. DOI: 10.11665/j.issn.1000-5048.20160303
Citation: RUAN Xiaoling, ZHENG Xiangyuan, XU Jie, DING Li, ZHENG Feng. Advances in analytical techniques for the determination of genotoxic impurities in pharmaceuticals[J]. Journal of China Pharmaceutical University, 2016, 47(3): 267-274. DOI: 10.11665/j.issn.1000-5048.20160303
shu

Advances in analytical techniques for the determination of genotoxic impurities in pharmaceuticals

More Information
    Graphical Abstract
    • Abstract
  • Genotoxic or potentially genotoxic impurities seriously threaten people′s health, therefore, it is necessary to identify and quantify these impurities in pharmaceutical materials even at trace levels. Due to the special requirements on the sensitivity, selectivity, analyte stability and matrix effect, development of analytical methods is a challenge for the determination of genotoxic impurities. This paper reviews the recent advances in analytical methods for trace levels of commonly encountered genotoxic or potentially genotoxic impurities, including alkyl halides, alkyl sulfonates, hydrazines, epoxides and acyl halides, which would be helpful to control these impurities.
    • FullText(HTML)
    • References (51)
  • [1]
    Bouder F.Regulating impurities in pharmaceutical products:a tolerability of risk approach[J].Expert Rev Clin Pharmacol,2008,1(2):241-250.
    [2]
    Mueller L,Mauthe RJ,Riley CM,et al.A rationale for determining,testing,and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity[J].Regul Toxicol Pharmacol,2006,44(3):198-211.
    [3]
    Committee for Medicinal Products for Human Use(CHMP).Guidelines on the limits of genotoxic impurities(CPMP/SWP/5199/02)[S].London:European Medicines Agency Evaluation of Medicines for Human Use(EMEA),2006.
    [4]
    U.S.Food and Drug Administration,Department of Health and Human Services,Center for Drug Evaluation and Research(CDER).Guidance for industry:genotoxic and carcinogenic impurities in drug substances and products:recommended approaches(draft)[S].Silver Spring:U.S.Food and Drug Administration,2008.
    [5]
    Benigni R,Bossa C,Tcheremenskaia O,et al.Development of structural alerts for the in vivo micronucleus assay in rodents,EUR 23844 EN[R].Luxenbourg:Office for the Official Publications of the European Communities,2009.
    [6]
    Benigni R,Bossa C.Mechanisms of chemical carcinogenicity and mutagenicity:a review with implications for predictive toxicology[J].Chem Rev,2011,111(4):2507-2536.
    [7]
    Skett PW,Smith RJ,Webb ML.Low level measurement of potent toxins[M]//Smith RJ,Webb ML.Analysis of Drug Impurities.Oxford:Blackwell Publishing,2007:82-123.
    [8]
    Wang Y.Determination of organic volatile impurities in azasetron hydrochloride[J].Chin J Pharm Anal(药物分析杂志),2004,24(3):293-295.
    [9]
    Liu DQ,Sun M,Kord AS.Recent advances in trace analysis of pharmaceutical genotoxic impurities[J].J Pharm Biomed Anal,2010,51(5):999-1014.
    [10]
    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):1097-1103.
    [11]
    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,2014,1361:217-228.
    [12]
    Lee KC,Cheuk MW,Chan W,et al.Determination of glucosinolates in traditional Chinese herbs by high-performance liquid chromatography and electrospray ionization mass spectrometry[J].Anal Bioanal Chem,2007,386(7/8):2225-2232.
    [13]
    Venugopal N,Reddy AVB,Madhavi G,et al.Trace level quantification of 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine HCl genotoxic impurity in trazodone using LC-MS/MS[J].Arab J Chem,2014,575:1-8.
    [14]
    Cappiello A,Famiglini G,Palma P,et al.A new liquid chromatography-mass spectrometry approach for generic screening and quantitation of potential genotoxic alkylation compounds without derivatization[J].J Pharm Biomed Anal,2012,1255(17):286-290.
    [15]
    van Wijk AM,Niederländer HA,Siebum AH,et al.A new derivatization reagent for LC-MS/MS screening of potential genotoxic alkylation compounds[J].J Pharm Biomed Anal,2013,74(4):133-140.
    [16]
    van Wijk AM,Niederländer HA,van Ogten MD,et al.Sensitive CE-MS analysis of potentially genotoxic alkylation compounds using derivatization and electrokinetic injection[J].Anal Chimi Acta,2015,874:75-83.
    [17]
    Raman NV,Prasad AV,Reddy KR,et al.Sensitive derivatization methods for the determination of genotoxic impurities in drug substances using hyphenated techniques[J].J Pharm Biomed Anal,2014,89:276-281.
    [18]
    Harigaya K,Yamada H,Yaku K,et al.Novel sensitive determination method for a genotoxic alkylating agent,4-chloro-1-butanol,in active pharmaceutical ingredients by LC-ICP-MS employing iodo derivatization[J].Anal Sci,2014,30(3):377-382.
    [19]
    Li W.Trace analysis of residual methyl methanesulfonate,ethyl methanesulfonate and isopropyl methanesulfonate in pharmaceuticals by capillary gas chromatography with flame ionization detection[J].J Chromatogr A,2004,1046(1/2):297-301.
    [20]
    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):201-204.
    [21]
    Ramakrishna K,Raman NV,Rao KM,et al.Developmentand validation of GC-MS method for the determination of methyl methanesulfonate and ethyl methanesulfonate in imatinib mesylate[J].J Pharm Biomed Anal,2008,46(4):780-783.
    [22]
    Raman NV,Prasad AV,Reddy KR,et al.Determination of genotoxic alkyl methane sulfonates and alkyl paratoluene sulfonates in lamivudine using hyphenated techniques[J].J Pharm Anal,2012,2(4):314-318.
    [23]
    Raman NV,Reddy KR,Prasad AV,et al.Development and validation of RP-HPLC method for the determination of genotoxic alkyl benzenesulfonates in amlodipine besylate[J].J Pharm Biomed Anal,2008,48(1):227-230.
    [24]
    García A,Rupérez FJ,Ceppa F,et al.Development of chromatographic methods for the determination of genotoxic impurities in cloperastine fendizoate[J].J Pharm Biomed Anal,2012,61(5):230-236.
    [25]
    Kakadiya PR,Reddy BP,Singh V,et al.Low level determinations of methyl methanesulfonate and ethyl methanesulfonate impurities in lopinavir and ritonavir active pharmaceutical ingredients by LC/MS/MS using electrospray ionization[J].J Pharm Biomed Anal,2011,55(2):379-384.
    [26]
    Guo T,Shi YY,Zheng L,et al.Rapid and simultaneous determination of sulfonate ester genotoxic impurities in drug substance by liquid chromatography coupled to tandem mass spectrometry:comparison of different ionization modes[J].J Chromatogr A,2014,1355:73-79.
    [27]
    European Directorate for Quality and Medicines&HealthCare(EDQM).Methyl,ethyl and isopropyl methanesulfonate in methanesulfonic acid[S]//European Pharmacopoeia 8.0.Strasbourg:Council of Europe,2011.
    [28]
    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 Anal,2005,39(3/4):477-485.
    [29]
    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):857-863.
    [30]
    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 Anal,2007,45(3):472-479.
    [31]
    European Directorate for Quality and Medicines&HealthCare(EDQM).Methyl,ethyl and isopropyl methanesulfonate in active substances[S]//European Pharmacopoeia 8.0.Strasbourg:Council of Europe,2012.
    [32]
    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 Anal,2008,48(3):1006-1010.
    [33]
    Reddy VB,Venugopal N,Madhavi G.A selective and sensitive LC-MS/MS method for the simultaneous determination of two potential genotoxic impurities in celecoxib[J].J Anal Sci Technol,2014,5(1):1-8.
    [34]
    Lakshmi KJ,Devi PR,Mukkanti K.Quantitative determination of residual hydrazine content in cilazapril by ion chromatography[J].Orient J Chem,2010,26(3):1001-1006.
    [35]
    Kean T, Miller JH, Skellern GG, et al. Acceptance criteria for levels of hydrazine in substances for pharmaceutical use and analytical methods for its determination[J].Pharmeur Sci Notes,2006(2):23-33.
    [36]
    Liu M,Ostovic J,Chen EX,et al.Hydrophilic interaction liquid chromatography with alcohol as a weak eluent[J].J Chromatogr A,2009,1216(12):2362-2370.
    [37]
    Matsui F,Robertson DL,Lovering EG.Determination of hydrazine in pharmaceuticals III:hydralazine and isoniazid using glc[J].J Pharm Sci,1983,72(8):948-951.
    [38]
    Sun M,Bai L,Terfloth GJ,et al.Matrix deactivation:a general approach to improve stability of unstable and reactive pharmaceutical genotoxic impurities for trace analysis[J].J Pharm Biomed Anal,2010,52(1),30-36.
    [39]
    Oh JA,Park JH,Shin HS.Sensitive determination of hydrazine in water by gas chromatography-mass spectrometry after derivatization with ortho-phthalaldehyde[J].Anal Chim Acta,2013,769(6):79-83.
    [40]
    Oh JA,Shin HS.Simple and sensitive determination of hydrazine in drinking water by ultra-high-performance liquid chromatography-tandem mass spectrometry after derivatization with naphthalene-2,3-dialdehyde[J].J Chromatogr A,2015,1395:73-78.
    [41]
    Klick S.Evaluation of different injection techniques in the gas chromatographic determination of thermo labile trace impurities in a drug substance[J].J Pharm Biomed Anal,1995,13(4/5):563-566.
    [42]
    Xiao KP,Xiong Y,Liu FZ,et al.Efficient method development strategy for challenging separation of pharmaceutical molecules using advanced chromatographic techniques[J].J Chromatogr A,2007,1163(1/2):145-156.
    [43]
    Rao RN,Raju AN,Narshima R.Isolation and characterization of process related impurities an degradation products of bicalutamide and development of RP-HPLC method for impurity profile study[J].J Pharm Biomed Anal,2008,46(3):505-519.
    [44]
    Spangler M,Mularz E.A validated,stability-indicating method for the assay of dexamethasone in drug substance and drug product analyses,and the assay of preservatives in drug product[J].Chromatographia,2001,54(5):329-334.
    [45]
    Petkovska R,Cornett C,Dimitrovska A.Development and validation of rapid resolution RP-HPLC method for simultaneous determination of atorvastatin and related compounds by use of chemometrics[J].Anal Lett,2008,41(6):992-1009.
    [46]
    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):302-306.
    [47]
    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):1106-1111.
    [48]
    Khan SJ,Weinberg HS,Bedford EC.Aqueous-phase aminolysis:approach for the analysis of epoxides in water[J].Anal Chem,2006,78(8):2608-2616.
    [49]
    Khan M,Jayasree K,Reddy KV,et al.A validated CE method for determining dimethylsulfate a carcinogen and chloroacetyl chloride a potential genotoxin at trace levels in drug substances[J].J Pharm Biomed Anal,2012,58(2):27-33.
    [50]
    Fu M,Lu Q,Hewitt E,et al.Ultra high performance liquid chromatography coupled with high resolution quantitation mass spectrometry method development and validation for determining genotoxic 2,5-dichlorobenzoyl chloride in MLN9708 drug substance[J].J Pharm Biomed Anal,2014,89(4):233-239.
    [51]
    Tang L,Kim A,Miller SA,et al.Development and validation of a specific and sensitive GC-FID method for the determination of impurities in 5-chlorovaleroyl chloride[J].J Pharm Biomed Anal,2010,53(3):309-314.
    • Related Articles

  • Related Articles

    [1]YE Zhenning, WU Zhenghong, ZHANG Huaqing. Research progress of blood-brain barrier crossing strategies and brain-targeted drug delivery mediated by nano-delivery system[J]. Journal of China Pharmaceutical University, 2024, 55(5): 590-602. DOI: 10.11665/j.issn.1000-5048.2024052202
    [2]LUO Xuelian, WU Chengsheng, ZHA Cheng, LIU Sheng. Research progress and prospects of implantable drug delivery systems for postoperative tumor therapy[J]. Journal of China Pharmaceutical University, 2024, 55(4): 538-547. DOI: 10.11665/j.issn.1000-5048.2024040901
    [3]WANG Shihao, LIU Lifeng, DING Yang, LI Suxin. Research progress of pH-responsive drug delivery systems in cancer immunotherapy[J]. Journal of China Pharmaceutical University, 2024, 55(4): 522-529. DOI: 10.11665/j.issn.1000-5048.2024011902
    [4]YU Jiayu, LIN Zezhi, CAO Wei, ZHANG Jianjun, WEI Yuanfeng, GAO Yuan, QIAN Shuai. Research progress of bio-metal organic frameworks in drug delivery system[J]. Journal of China Pharmaceutical University, 2023, 54(1): 23-33. DOI: 10.11665/j.issn.1000-5048.20221111003
    [5]ZHOU Yeshu, WANG Yanmei, ZHANG Beiyuan, WU Shuaicong, YANG Lei, YIN Lifang. Research progress of inorganic nanomaterials in drug delivery system[J]. Journal of China Pharmaceutical University, 2020, 51(4): 394-405. DOI: 10.11665/j.issn.1000-5048.20200403
    [6]LI Haoxian, LIN Huaqing, CHEN Jingwen, WANG Liyuan. Research progress of carbon nanomaterials in cancer drug delivery[J]. Journal of China Pharmaceutical University, 2019, 50(1): 100-106. DOI: 10.11665/j.issn.1000-5048.20190114
    [7]FAN Qianqian, XING Lei, QIAO Jianbin, ZHANG Chenglu, JIANG Hulin. Advances in drug delivery systems for the treatment of liver fibrosis[J]. Journal of China Pharmaceutical University, 2018, 49(3): 263-271. DOI: 10.11665/j.issn.1000-5048.20180302
    [8]CHEN Xing, KANG Yang, WU Jun. Advances in biodegradable functional polymers based protein drug delivery system[J]. Journal of China Pharmaceutical University, 2017, 48(2): 142-149. DOI: 10.11665/j.issn.1000-5048.20170203
    [9]WANG Yazhe, ZHOU Jianping, DING Yang, WANG Wei. Advances in research of biomimetic drug delivery systems[J]. Journal of China Pharmaceutical University, 2014, 45(3): 267-273. DOI: 10.11665/j.issn.1000-5048.20140303
    [10]TANG Yue, KE Xue. Advances of mesoporous silica nanoparticles as drug delivery system[J]. Journal of China Pharmaceutical University, 2012, 43(6): 567-572.

  • Cited by

    Periodical cited type(9)

    1. 蔡鸿飞，张琴，关伟键，杨阳，袁诚，许文东. 不同干燥方式对灵芝孢子粉中灵芝孢子油过氧化值的影响. 广东化工. 2024(01): 28-30 .
    2. 林志彬. 灵芝孢子油的药效物质基础研究进展. 菌物研究. 2024(01): 79-87 .
    3. Jianying Liu，Binzhi Zhang，Leqi Wang，Shasha Li，Qinqiang Long，Xue Xiao. Bioactive components, pharmacological properties and underlying mechanism of Ganoderma lucidum spore oil: A review. Chinese Herbal Medicines. 2024(03): 375-391 .
    4. 武美华，张胜男，敬隆鑫，律凤霞. 灵芝的活性成分及其药理作用的研究进展. 中国林副特产. 2023(02): 76-79 .
    5. 夏凤娜，关小莺，陈少丹，陈秋颜，张一帆，杨小兵. 灵芝孢子粉脂质成分HPLC-ELSD指纹图谱构建及含量测定. 食用菌学报. 2023(06): 52-59 .
    6. 井子良，吴纯宇，张慧敏，孙建博. 灵芝孢子油番茄红素复合物的抗肿瘤作用. 现代食品科技. 2022(09): 46-51 .
    7. 李志强，何玉霞. 灵芝多糖对人肺癌A549细胞增殖凋亡的作用. 现代食品科技. 2021(05): 38-42 .
    8. 张琴，李康强，杨阳，张圳，蔡鸿飞，许文东. 不同提取方式的灵芝孢子油品质研究. 广东化工. 2021(11): 48-49 .
    9. 包县峰，徐勇，刘维明，王星丽，孙培龙，张安强. 灵芝孢子粉生物活性成分及药理作用. 食品工业科技. 2020(06): 325-331 .

    Other cited types(6)

Catalog

    Get Citation
    PDF
    XML
    Article views PDF downloads Cited by(15)
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：286500

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return