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The determination of cyclophosphamide and its metabolites in blood plasma as stable trifluoroacetyl derivatives by electron capture chemical ionization gas chromatography/mass spectrometry.

Abstract
A method is described for the determination of the antitumour drug cyclophosphamide and six stable metabolites in plasma of cancer patients, namely dechloroethyl-cyclophosphamide, 4-keto-cyclophosphamide, carboxy-phosphamide, alcophosphamide, nor-nitrogen mustard and the N-chloroethyl-1,3-oxazolidine-2-one, as methyl and/or trifluoroacetyl derivatives by single ion monitoring gas chromatography/mass spectrometry, mostly in the electron capture chemical ionization mode. The isolation of most metabolites was performed by solid-phase C-18 extraction in weakly acidic medium. The phosphoramide mustard isolated under these conditions decomposes readily to the nor-nitrogen mustard during derivatization. The original nor-nitrogen mustard and the chloroethyl-1,3-oxazolidine-2-one were isolated by liquid extraction with ethyl acetate in alkaline medium. Recoveries of 75-99% were measured using spiked blank plasma samples. Quantitation of metabolites in patient plasma samples was performed using two sets of calibration curves for the concentration ranges of 1-100 ng and 0.1-10 micrograms of metabolite per millilitre of original plasma.
AuthorsG Momerency, K Van Cauwenberghe, P H Slee, A T Van Oosterom, E A De Bruijn
JournalBiological mass spectrometry (Biol Mass Spectrom) Vol. 23 Issue 3 Pg. 149-58 (Mar 1994) ISSN: 1052-9306 [Print] England
PMID8148406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • Oxazoles
  • Oxazolidinones
  • Phosphoramide Mustards
  • N-chloroethyl-1,3-oxazolidin-2-one
  • dechloroethylcyclophosphamide
  • alcophosphamide
  • Cyclophosphamide
  • carboxyphosphamide
  • nornitrogen mustard
  • 4-ketocyclophosphamide
Topics
  • Antineoplastic Agents (therapeutic use)
  • Cyclophosphamide (analogs & derivatives, blood, therapeutic use)
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Neoplasms (drug therapy)
  • Nitrogen Mustard Compounds (blood)
  • Oxazoles (blood)
  • Oxazolidinones
  • Phosphoramide Mustards (blood)

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