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

✍ Scribed by G. Momerency; K. Van Cauwenberghe; P. H. Th. J. Slee; A. T. Van Oosterom; E. A. De Bruijn

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 723 KB
• Volume: 23
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/bms.1200230306

✦ Synopsis

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-cyclophosphamiide, carboxyphosphamide, alcophosphamide, nor-nitrogen mustard and the N-chloroethyl-l,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 7549% 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 pg of metabolite per millilitre of original plasma.