Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC-ESI-QTOFMS-based metabolomics.
Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC-ESI-QTOFMS-based metabolomics.
复制标题
DOI：
10.1016/j.bcp.2010.06.002
复制
发表时间：
2010-10-01
影响因子：
5.8
通讯作者：
Idle, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Li, Fei;Patterson, Andrew D.;Hoefer, Constance C.;Krausz, Kristopher W.;Gonzalez, Frank J.;Idle, Jeffrey R.
关键词：
Ifosfamide (IF) and cyclophosphamide (CP) are common chemotherapeutic agents. Interestingly, while the two drugs are isomers, only IF treatment is known to cause nephrotoxicity and neurotoxicity. Therefore, it was anticipated that a comparison of IF and CP drug metabolites in the mouse would reveal reasons for this selective toxicity. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), and the results analyzed by multivariate data analysis. Of the total 23 drug metabolites identified by UPLC-ESI-QTOFMS for both IF and CP, five were found to be novel. Ifosfamide preferentially underwent N-dechloroethylation, the pathway yielding 2-chloroacetaldehyde, while cyclophosphamide preferentially underwent ring-opening, the pathway yielding acrolein (AC). Additionally, S-carboxymethylcysteine and thiodiglycolic acid, two downstream IF and CP metabolites, were produced similarly in both IF- and CP-treated mice. This may suggest that other metabolites, perhaps precursors of thiodiglycolic acid, may be responsible for IF encephalopathy and nephropathy.
登录
查看更多内容
DOI：
10.1124/jpet.106.105213
发表时间：
2006-09-01
影响因子：
3.5
作者：
Chen, Chi;Meng, Linghua;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.
影响因子：
8.4
作者：
BODDY, AV;PROCTOR, M;IDLE, JR
通讯作者：
IDLE, JR
DOI：
10.1007/bf01471475
发表时间：
1952-01-01
期刊：
KLINISCHE WOCHENSCHRIFT
影响因子：
--
作者：
DRUCKREY, H;RAABE, S
通讯作者：
RAABE, S
影响因子：
4.1
作者：
Chen, Chi;Ma, Xiaochao;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.
影响因子：
3
作者：
Boddy, AV;Yule, SM;Idle, JR
通讯作者：
Idle, JR