title: 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.
authors.affiliation: Department of Chemistry, University of Antwerp (UIA), Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Momerency
authors.forename: K
authors.initials: K
authors.lastname: Van Cauwenberghe
authors.forename: P H
authors.initials: PH
authors.lastname: Slee
authors.forename: A T
authors.initials: AT
authors.lastname: Van Oosterom
authors.forename: E A
authors.initials: EA
authors.lastname: De Bruijn
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000097:blood; D010080:Oxazoles / Q000097:blood*; D023303:Oxazolidinones; D010752:Phosphoramide Mustards / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D010080:Oxazoles; D023303:Oxazolidinones; D010752:Phosphoramide Mustards; C086633:N-chloroethyl-1,3-oxazolidin-2-one; C064445:dechloroethylcyclophosphamide; C052572:alcophosphamide; D003520:Cyclophosphamide; C000028:carboxyphosphamide; C004933:nornitrogen mustard; C008226:4-ketocyclophosphamide