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使用离子簇技术鉴定大鼠尿液中磷酰胺、去氮氮芥和环磷酰胺的新代谢物。

Identification of new metabolites of phosphoramide and nor-nitrogen mustards and cyclophosphamide in rat urine using ion cluster techniques.

作者信息

Chan K K, Hong S C, Watson E, Deng S K

出版信息

Biomed Environ Mass Spectrom. 1986 Mar;13(3):145-54. doi: 10.1002/bms.1200130310.

DOI:10.1002/bms.1200130310
PMID:2938656
Abstract

The metabolism of nor-nitrogen (NNM) and phosphoramide mustards (PM) and cyclophosphamide (CP) was investigated in the Sprague-Dawley rat using chemical ionization mass spectrometry and ion cluster techniques. Following administrations of a 1:1 mixture of the non-labeled and the corresponding side-chain deuterium-labeled compounds to separate rats, the urinary extracts were screened for cluster ions which were characteristic of the administered compounds and their derived metabolites, and on this basis, tentative identifications of known and new metabolites were accomplished. Combining derivatization, deuterium labeling on strategic locations, gas chromatography/mass spectrometry, and chemical synthesis in some cases, 3-(2-chloroethyl)-1,3-oxazolidin-2-one was identified as a major metabolite for NNM, PM and CP and 3-(2-chloroethyl)-4-hydroxy-1,3-oxazolidin-2-one was identified as a major metabolite for NNM and PM, but a minor metabolite for CP. A new dechlorinated metabolite for CP, 3-(2-hydroxyethyl)-1,3-oxazolidin-2-one, was also identified.

摘要

使用化学电离质谱法和离子簇技术,在斯普拉格-道利大鼠中研究了去甲氮芥(NNM)、磷酰胺氮芥(PM)和环磷酰胺(CP)的代谢情况。在将未标记的化合物与相应的侧链氘标记化合物以1:1的混合物分别给予大鼠后,对尿液提取物进行筛选,寻找作为所给药化合物及其衍生代谢物特征的簇离子,并在此基础上对已知和新的代谢物进行了初步鉴定。结合衍生化、关键位置的氘标记、气相色谱/质谱法以及某些情况下的化学合成,3-(2-氯乙基)-1,3-恶唑烷-2-酮被鉴定为NNM、PM和CP的主要代谢物,3-(2-氯乙基)-4-羟基-1,3-恶唑烷-2-酮被鉴定为NNM和PM的主要代谢物,但为CP的次要代谢物。还鉴定出一种CP的新的脱氯代谢物,即3-(2-羟乙基)-1,3-恶唑烷-2-酮。

相似文献

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Identification of new metabolites of phosphoramide and nor-nitrogen mustards and cyclophosphamide in rat urine using ion cluster techniques.使用离子簇技术鉴定大鼠尿液中磷酰胺、去氮氮芥和环磷酰胺的新代谢物。
Biomed Environ Mass Spectrom. 1986 Mar;13(3):145-54. doi: 10.1002/bms.1200130310.
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Kinetics of hydrolysis in vitro of nornitrogen mustard, a metabolite of phosphoramide mustard and cyclophosphamide.
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Kinetics of hydrolysis in vitro of nornitrogen mustard, a metabolite of phosphoramide mustard and cyclophosphamide.
Arch Toxicol. 1987 Dec;61(2):126-30. doi: 10.1007/BF00661370.