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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
 

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UHPLC-MS法测定2种硫酸氢氯吡格雷晶型中的基因毒性杂质对甲苯磺酸甲酯

Determination of genotoxic impurity methyl p-toluenesulfonate in two kinds of crystal forms of clopidogrel hydrogen sulfate

作者(英文):
分类号:R917
出版年·卷·期(页码):2017,37 (11):1994-1999
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:建立超高效液相色谱-三重四极杆质谱联用法(UHPLC-MS)测定2种硫酸氢氯吡格雷晶型(Ⅰ型和Ⅱ型)中基因毒性杂质对甲苯磺酸甲酯。方法:采用Zorbax Extend C18(2.1 mm×50 mm,1.8 μm)色谱柱,以0.1%甲酸水溶液为流动相A,0.1%甲酸甲醇溶液为流动相B,梯度洗脱,流速为0.4 mL·min-1,电喷雾(ESI)正离子检测模式,采用多反应监测(MRM)扫描模式,选择m/z 187→91作为定量离子对,m/z 187→155作为定性离子对。结果:对甲苯磺酸甲酯质量浓度在1.0~200 ng·mL-1范围内线性关系良好(r=0.999 9);检测限为0.5 ng·mL-1;定量限为1.0 ng·mL-1;Ⅰ型晶型和Ⅱ型晶型的加样回收率分别为97.7%和97.9%(n=9),RSD分别为1.5%和1.5%;4℃控温条件下供试品溶液在48 h内稳定性良好(RSD=1.6%);2种晶型各3批样品中均未检出对甲苯磺酸甲酯。结论:本方法结果可靠,可以用于硫酸氢氯吡格雷原料中对甲苯磺酸甲酯的检测。

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

Objective: To determine genotoxic impurity methyl p-toluenesulfonate in two kinds of crystal forms(crystal form I and crystal form Ⅱ) of clopidogrel hydrogen sulfate by UHPLC-MS;Methods: The separation was performed on a Zorbax Extend C18 column(2.1 mm×50 mm, 1.8 μm) with the mobile phase consisting of 0.1% formic acid aqueous solution(mobile phase A) and 0.1% formic acid methanol(mobile phase B) by gradient elution at a flow rate of 0.4 mL·min-1.Multiple reaction monitoring(MRM) was performed on a triple quadrupole mass spectrometer equipped with a ESI source in the positive mode, selecting m/z 187→91 as the quantitative ion pair and m/z 187→155 as qualitative ion pair.Results: The calibration curve was in a good linearity within the range of 1.0-200 ng·mL-1(r=0.999 9).The limit of detection was 0.5 ng·mL-1.The limit of quantification was 1.0 ng·mL-1.The spike recovery of the two crystal forms were 97.7% and 97.9%(n=9), with RSD of 1.5% and 1.5%, respectively.The sample solution was stable under 4℃ within 48 hours(RSD=1.6%).Methyl p-toluenesulfonate was not detected in sample solutions of two crystal forms.Conclusion: The method is accurate and reliable to determine methyl p-toluenesulfonate in clopidogrel hydrogen sulfate substance.

-----参考文献:---------------------------------------------------------------------------------------
[1] LU J,WANG J,ROHANI S.Preparation and characterization of amorphous,I andⅡ forms of clopidogrel hydrogen sulfate[J].Cryst Res Technol,2012,47(5):505
[2] 梁美好,沈正荣.(+)-氯吡格雷的合成工艺改进[J].中国药物化学杂志,2007,17(3):163 LIANG MH,SHEN ZR.Improved synthesis of clopidogrel[J].Chin J Med Chem,2007,17(3):163
[3] SZEKELY G,AMORES MC,GIL M,et al.Genotoxic impurities in pharmaceutical manufacturing:Sources,regulations,and mitigation.Chem Rev,2015,115(16):8182
[4] EUROPEAN MEDICINES AGENCY.Guidelines on the limits of genotoxicimpurities[EB/OL].[2016-12-05].http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002903.pdf
[5] US FOOD AND DRUG ADIMMINISTRATION.Guidance for industry.Genotoxic and carcinogenic impurities in drug substances and products:recommended approaches[EB/OL].[2016-12-05].http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0629-gdl.pdf
[6] GUO T,SHI Y,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
[7] 张云峰,钱建钦,王建.HPLC-MS/MS法分析氟胞嘧啶中痕量基因毒性杂质N,N-二甲基苯胺[J].药物分析杂志,2017,37(2):265 ZHANG YF,QIAN JQ,WANG J.Determination of trace level of genotoxic impurity N,N-dimethylaniline in flucytosine by HPLC-MS/MS[J].Chin J Pharm Anal,2017,37(2):265
[8] 陈菁菁,杨小玲,李琴.UPLC-QTOF/MS法分析盐酸奈必洛尔中痕量遗传毒性杂质A和B[J].药物分析杂志,2016,36(11):2035 CHEN JJ,YANG XL,LI Q.Trace determination of genotoxic impurities A and B in nebivolol hydrochloride by UPLC-QTOF/MS[J].Chin J Pharm Anal,2016,36(11):2035
[9] 沈雨婷,马迅,南楠.UPLC-MS/MS方法测定盐酸哌替啶原料及注射液中的神经毒性杂质1-甲基-4-苯基-1,2,3,6-四氢吡啶[J].药物分析杂志,2016,36(5):911 SHEN YT,MA X,NAN N. Determination of neurotoxicity impurity MPTP in pethidine hydrochloride API and injection by UPLC-MS/MS[J].Chin J Pharm Anal,2016,36(5):911
[10] 钱建钦,陈悦.正负离子切换超高效液相色谱-质谱联用法同时测定达比加群酯中间体中的2个毒性杂质[J].中国药学杂志,2016,51(11):930 QIAN JQ,CHEN Y.Simultaneous determination of two toxic impurities in the intermediate of dabigatranetexilate by UHPLC-MS with positive/negative ionization switching[J].Chin Pharm J,2016,51(11):930
[11] 白培锋,李海霞,郭文敏.LC-MS/MS法检测奥拉帕尼中的遗传毒性杂质[J].中国新药杂志,2016,25(8):865 BAI PF,LI HX,GUO WM.High sensitive determination of the genotoxic impurities in olaparib by LC-MS/MS[J].Chin J New Drugs,2016,25(8):865
[12] 李海霞,白培锋,刘娜,等.卡非佐米中基因毒性杂质和吗啉乙酸的LC-MS/MS法测定[J].中国医药工业杂志,2016,47(11):1308 LI HX,BAI PF,LIU N,et al.Determination of a genotoxic impurity and morpholin acetic acid in carfilzomib by LC-MS/MS[J].Chin J Pharm,2016,47(11):1308
[13] 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 ZHOU CP,WANG DW,ZHANG MY,et al.Determination of two genotoxic impurities residues in dronedarone hydrochloride by HPLC-QTRAP-MS/MS[J].J Instrm Anal,2016,35(9):1111
[14] 王慧君,潘红娟,刘超,等.阿哌沙班中基因毒性杂质的LC-MS法测定[J].中国医药工业杂志,2015,46(9):1004 WANG HJ,PAN HJ,LIU C,et al.Determination of the gnotoxic impurity in apixaban by LC-MS[J].Chin J Pharm,2015,46(9):1004
[15] 梁键谋,傅聪,陈悦,等.LC-MS/MS测定草酸右旋西酞普兰中对甲苯磺酸酯类基因毒性杂质的含量[J].中国现代应用药学,2016,33(11):1436 LIANG JM,FU C,CHEN Y.Determination of genotoxic impurities in escitalopram oxalate by LC-MS/MS[J].Chin J Mod Appl Pharm,2016,33(11):1436
[16] 张莉,黄丽娜,黎其荣,等.HPLC-MS法分析甲苯磺酸拉帕替尼中痕量基因毒性杂质[J].药物分析杂志,2015,35(2):317 ZHANG L,HUANG LN,LI QR,et al.Trace determination of genotoxic impurity in lapatinibditosylate by HPLC-MS[J].Chin J Pharm Anal,2015,35(2):317
[17] 冯慧敏,杭太俊,高新桃,等.LC-MS法同时检测甲磺酸伊马替尼中3个磺酸酯基因毒杂质[J].药物分析杂志,2014,34(12):2202 FENG HM,HANG TJ,GAO XT,et al.Determination of potential carcinogenic and genotoxic sulfonate impurities in imatinib mesylate by a highly sensitive liquid chromatography-mass spectrometry method[J].Chin J Pharm Anal,2014,34(12):2202

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