The N-dechloroethylation of ifosfamide: using stereochemistry to obtain an accurate picture of a clinically relevant metabolic pathway

Cancer Chemother Pharmacol. 1996;37(4):332-6. doi: 10.1007/s002800050393.


The cumulative urinary excretions of the enantiomers of ifosfamide [(R)-IFF, (S)-IFF)] and their 2-N-dechlorethylated (2-DCE-IFF) and 3-N-dechloroethylated (3-DCE-IFF) metabolites were determined in 11 adult cancer patients who received a single 3-h infusion of IFF (3 g/m2) with mesna uroprotection. The urine samples were analyzed for the compounds of interest using an enantioselective gas chromatographic-mass spectrometric assay. The results indicated an enantioselective excretion of the parent and N-dechloroethylated metabolites: the urinary recovery of (R)-IFF was significantly greater than that of (S)-IFF (1.73 +/- 0.45 vs 1.43 +/- 0.41 mmol, P < 0.0001); the excretion of (S)-2-DCE-IFF (0.75 +/- 0.53 mmol) was greater than that of (R)-2-DCE-IFF (0.42 +/- 0.22 mmol, P = 0.071) while the excretion of (R)-3-DCE-IFF (1.64 +/- 0.76 mmol) was greater than that of (S)-3-DCE-IFF (0.77 +/- 0.59 mmol, P = 0.012). The study also revealed two distinct metabolic patterns in which the urinary recoveries of (R)-2-DCE-IFF and (R)-3-DCE-IFF were linked as were those of (S)-2-DCE-IFF and (S)-3-DCE-IFF. The results suggest that at least two enzymes are involved in the N-dechlorethylation of IFF. The data also demonstrate the importance of following the metabolic fate of (R)-IFF and (S)-IFF and of determining the relative urinary excretion of all dechloroethylated metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biotransformation
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / chemistry
  • Ifosfamide / pharmacokinetics*
  • Infusions, Intravenous
  • Pelvic Neoplasms / drug therapy
  • Pelvic Neoplasms / urine*
  • Recurrence
  • Stereoisomerism


  • Ifosfamide