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Identification of new metabolites of ifosfamide in rat urine using ion cluster technique
Author(s) -
Wang Jeff J.H.,
Chan Kenneth K.
Publication year - 1995
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1190300504
Subject(s) - chemistry , metabolite , ifosfamide , derivatization , chromatography , chemical ionization , mass spectrometry , hydroxylation , adduct , urine , metabolic pathway , metabolism , biochemistry , organic chemistry , ion , ionization , medicine , enzyme , surgery , chemotherapy , etoposide
Metabolism of the anticancer drug ifosfamide was investigated in Sprague‐Dawley rats. Along with four known metabolites, namely N 2 ‐dechloroethylifosfamide, N 3 ‐dechloroethylifosfamide, alcoifosfamide and isophosphoramide mustard, four new urinary metabolites were identified utilizing combined techniques of chemical modification/derivatization, capillary gas chromatography/chemical ionization mass spectrometry (ammonia), deuterium‐labeling/ion cluster analysis and chemical synthesis. Secondary metabolites of N 2 ‐dechloroethyl and N 3 ‐dechloroethylifosfamide formed by 4‐hydroxylation, i.e. 4‐hydroxy‐ N 2 ‐dechloroethylifosfamide and 4‐hydroxy‐ N 3 ‐dechloroethylifosfamide, respectively, and their subsequent decomposition product, N ‐dechloroethyliso‐phosphoramide mustard, were identified. Secondary dealkylation pathways of N 2 ‐dechloroethylifosfamide and/or N 3 ‐dechloroethylifosfamide were also demonstrated through characterization of N 2,3 ‐didechloroethyl ifosfamide. The key active metabolite of ifosfamide, 4‐hydroxyifosfamide, was characterized as a cyanohydrin adduct for the first time.