Identification of new metabolites of ifosfamide in rat urine using ion cluster technique

✍ Scribed by Jeff J.-H. Wang; Kenneth K. Chan

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 875 KB
• Volume: 30
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.1190300504

✦ Synopsis

Metabolism of the anticancer drug ifosfamide was investigated in SpragueDawley rats. Along with four known metabolites, namely p-dechloroethylifosfamide, M-dechloroethylifosfamide, alcoifosfamide and isophosphoramide mustard, four new urinary metabolites were identified utilizing combined techniques of chemical modificationfderivatization, capillary gas chromatography/chemical ionization mass spectrometry (ammonia), deuterium-labeling/ion cluster analysis and chemical synthesis. Secondary metabolites of p-dechloroethyl and A@-dechloroethylifosfamide formed by 4hydroxylation, ie. 4-hydroxy-p-dechloroethylifosfamide and 4hydroxy-Mdechloroethylifosfamide, respectively, and their subsequent decomposition product, Ndechloroethylisophosphoramide mustard, were identified. Secondary dealkylation pathways of p-dechloroethylifosfamide and/or Mdechloroethylifosfamide were also demonstrated through characterization of p*3didechloroethyl ifosfamide. The key active metabolite of ifosfamide, 4hydroxyifosfamide, was characterized as a cyanohydrin adduct for the first time.