[1]王立强,王凤玲,周玥莹,等.苯胺基喹唑啉类酪氨酸激酶抑制剂的电喷雾质谱裂解规律[J].华侨大学学报(自然科学版),2018,39(3):420-428.[doi:10.11830/ISSN.1000-5013.201706001]
　WANG Liqiang,WANG Fengling,ZHOU Yueying,et al.Fragmentation Pathways of Tyrosine Kinase Inhibitors With Anilinoquinazoline Moiety by Electrospray Ionization Mass Spectrometry[J].Journal of Huaqiao University(Natural Science),2018,39(3):420-428.[doi:10.11830/ISSN.1000-5013.201706001]
点击复制

苯胺基喹唑啉类酪氨酸激酶抑制剂的电喷雾质谱裂解规律()
分享到：

《华侨大学学报（自然科学版）》[ISSN:1000-5013/CN:35-1079/N]

卷:
第39卷
期数:
2018年第3期
页码:
420-428
栏目:
出版日期:
2018-05-20

文章信息/Info

Title:
Fragmentation Pathways of Tyrosine Kinase Inhibitors With Anilinoquinazoline Moiety by Electrospray Ionization Mass Spectrometry
文章编号:
1000-5013(2018)03-0420-09
作者:
王立强1;  王凤玲1;  周玥莹1;  李赞2;  高源2;  吴振2;  方美娟2
1. 华侨大学 生物医学学院, 福建 泉州 362021;2. 厦门大学 药学院, 福建 厦门 361000
Author(s):
WANG Liqiang1;  WANG Fengling1;  ZHOU Yueying1;  LI Zhan2;  GAO Yuan2;  WU Zhen2;  FANG Meijuan2
1. School of Biomedical Sciences, Huaqiao University, Quanzhou 362021, China; 2. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361000, China
关键词:
苯胺基喹唑啉;  酪氨酸激酶抑制剂;  电喷雾电离质谱;  裂解规律
Keywords:
anilinoquinazoline;  tyrosine kinase inhibitor;  electrospray ionization mass spectrometry;  fragmentation pathway
分类号:
R917
DOI:
10.11830/ISSN.1000-5013.201706001
文献标志码:
A
摘要:
研究吉非替尼、厄洛替尼和艾克替尼3种苯胺基喹唑啉类酪氨酸激酶抑制剂,在电喷雾质谱正离子模式下的裂解规律.通过电喷雾质谱产生各化合物稳定的［M+H］+准分子离子峰,进而对［M+H］+离子进行高能诱导裂解和碰撞诱导裂解,获得相应化合物的质谱图.结果表明:在电喷雾电离(ESI)多级质谱中,3种药物的裂解主要发生在喹唑啉环C4,C6和C7位取代基上,并伴随分子内重排和H+的迁移重排;在二级质谱图中,吉非替尼的高丰度特征离子质荷比(m/z)为128.1,厄洛替尼的m/z值为278.1和336.1,埃克替尼的m/z值为278.1,304.1.
Abstract:
The fragmentation pathways of three tyrosine kinase inhibitors with anilinoquinazoline moiety including gefitinib, erlotinib and icotinibwere analyzed by electrospray ionization tandem mass spectrometry in positive ion mode. The ［M+H］+ ions peaks were generated by electrospray ionization tandem mass spectrometry, and the subsequent product ions of ［M+H］+ ions information were obtained by using the higher energy collision induced dissociation and the collision induced dissociation. The results indicate that the fragmentation behavior mainly results from the cleavage of the C4, C6 and C7 substituent of the quinazoline ring, with intramolecular rearrangement and migration rearrangement of H+, and the high-abundance characteristic ions for gefitinib is m/z=128.1, for erlotinib are m/z=278.1 and m/z=336.1, and for icotinib are m/z=278.1 and m/z=304.1 in the secondary mass spectrum.

参考文献/References:

[1] ZHANG Jianming,YANG P L,GRAY N S.Targeting cancer with small molecule kinase inhibitors[J].Nature Reviews Cancer,2009,9(1):28-39.DOI:10.1038/nrc2559.
[2] ZHANG Yi,FICARRO S B,LI Shaojuan,et al.Optimized orbitrap HCD for quantitative analysis of phosphopeptides[J].Journal of American Society for Mass Spectrometry,2009,20(8):1425-1534.DOI:10.1016/j.jasms.2009.03.019.
[3] SEGU Z M,MECHREF Y.Characterizing protein glycosylation sites through higher-energy C-trap dissociation[J].Rapid Communication in Mass Spectrometry,2010,24(9):1217-1225.DOI:10.1002/rcm.4485.
[4] LANKHEET N A,HILLEBRAND M J,ROSING H,et al.Method development and validation for the quantification of dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma by liquid chromatography coupled with tandem mass spectrometry[J].Biomedical Chromatography,2013,27(4):466-476.DOI:10.1002/bmc.2814.
[5] WANG L Z,LIM M Y,CHIN T M,et al.Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry[J].Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences,2011,879(22):2155-2161.DOI:10.1016/j.jchromb.2011.05.056.
[6] COUCHMAN L,BIRCH M,IRELAND R,et al.An automated method for the measurement of a range of tyrosine kinase inhibitors in human plasma or serum using turbulent flow liquid chromatography-tandem mass spectrometry[J].Analytical and Bioanalytical Chemistry,2012,403(6):1685-1695.DOI:10.1007/s00216-012-5970-2.
[7] HOMEYWELL R,YARZADAH K,GIOVANNETTI,et al.Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry[J].Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences,2010,878(15/16):1059-1068.DOI:10.1016/j.jchromb.2010.03.010.
[8] SVEDBERG A,GREEN H,VIKSTROM A.A validated liquid chromatography tandem mass spectrometry method for quantification of erlotinib, OSI-420 and didesmethyl erlotinib and semi-quantification of erlotinib metabolites in human plasma[J].Journal Pharmaceutical and Biomedical Analysis,2015,107:186-195.
[9] LI Jing,ZHAO Ming,HE Ping,et al.Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes[J].Clinical Cancer Research,2007,13(12):3731-3737.DOI:10.1158/1078-0432.CCR-07-0088.
[10] GUAN Zhongmin,CHEN Xiaoyan,WANG Yinxiang,et al.Metabolite identification of a new antitumor agent icotinib in rats using liquid chromatography/tandem mass apectrometry[J].Rapid Communication in Mass Spectrometry,2008,22(14):2176-2184.DOI:10.1002/rcm.3599.

备注/Memo

备注/Memo:
收稿日期: 2017-06-09
通信作者: 王立强(1970-),男,教授,博士,主要从事药剂学和新药开发的研究.E-mail:wlq1599@163.com.
基金项目: 国家自然科学基金资助项目(81302652); 福建省自然科学基金资助项目(2015J01342)
更新日期/Last Update: 2018-05-20