A fragmentation-based method for the differentiation of glutathione conjugates by high-resolution mass spectrometry with electrospray ionization
文献类型：期刊论文
| 作者 | Xie, Cen ; Zhong, Dafang; Chen, Xiaoyan
|
| 刊名 | ANALYTICA CHIMICA ACTA
 |
| 出版日期 | 2013-07-25 |
| 卷号 | 788页码:89-98 |
| 关键词 | Glutathione conjugates Electrospray ionization-mass spectrometry Fragmentation pattern Detection Structural differentiation |
| ISSN号 | 0003-2670 |
| DOI | 10.1016/j.aca.2013.06.022 |
| 文献子类 | Article |
| 英文摘要 | Idiosyncratic reactions are one of the major causes of drug treatment limitations or market withdrawals, and likely involve the formation of reactive metabolites. Because of their unstable nature, reactive species are usually discovered as stable conjugates by glutathione (GSH) trapping rather than by direct detection. The GSH conjugates are then detected by neutral loss scanning of 129 Da or precursor ion scanning at m/z 272, but the conjugation sites can only be identified by comparison with reference standards. In the present study, the fragmentation behaviors of 52 GSH conjugates belonging to five structural classes (aliphatic, aromatic, benzylic, disulfide, and thioester) were investigated in both positive and negative electrospray ionization modes by high-resolution mass spectrometry with suitable collision energies such that the relative abundance of the parent ion was approximately 50% of the most abundant product ion. Several structural-diagnostic fragmentations were identified: aliphatic conjugates gave i/j-type ions upon cleavage of the C-S bond between the drug and GSH, and d/k-type ions formed by the cleavage of the cysteinyl C-S bond, with approximately equal intensity, in both positive and negative modes, whereas aromatic conjugates only possessed d/k-type ions, and benzylic conjugates primarily yielded i/j-type ions. Disulfide conjugates typically produced dehydrogenated GS-fragment ions ([i-2H]-type) in negative mode, and thioester conjugates displayed sequential losses of pyroglutamic acid and water ([e-H2O]-type) in positive mode. A fragmentation-based method was thus established to facilitate the discrimination of these five classes of GSH conjugates, thereby providing insight into the bioactivation mechanisms and supporting lead optimization. (C) 2013 Elsevier B.V. All rights reserved. |
| WOS关键词 | HUMAN LIVER-MICROSOMES ; IN-VITRO ; HUMAN HEPATOCYTES ; QUINONE METHIDE ; DRUG-REACTIONS ; IDENTIFICATION ; BIOACTIVATION ; METABOLITES ; ACID ; VIVO |
| 资助项目 | National Natural Science Foundation of China[81173115] ; National Basic Research Program of China[2009CB930300] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000321497700013 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277534]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Chen, Xiaoyan |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Cen,Zhong, Dafang,Chen, Xiaoyan. A fragmentation-based method for the differentiation of glutathione conjugates by high-resolution mass spectrometry with electrospray ionization[J]. ANALYTICA CHIMICA ACTA,2013,788:89-98. |
| APA | Xie, Cen,Zhong, Dafang,&Chen, Xiaoyan.(2013).A fragmentation-based method for the differentiation of glutathione conjugates by high-resolution mass spectrometry with electrospray ionization.ANALYTICA CHIMICA ACTA,788,89-98. |
| MLA | Xie, Cen,et al."A fragmentation-based method for the differentiation of glutathione conjugates by high-resolution mass spectrometry with electrospray ionization".ANALYTICA CHIMICA ACTA 788(2013):89-98. |
入库方式： OAI收割
来源：上海药物研究所
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