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Link to publicationCitation for published version (APA): Bruijn, de, E. A., Oosterom, van, A. T., Leclercq, P. A., Haan, de, J. W., Ven, van de, L. J. M., & Tjaden, U. R. (1987). Monitoring the behaviour of 4-ketocyclophosphamide versus cyclophosphamide during capillary gas chromatography by mass spectrometry. Biomedical & Environmental Mass Spectrometry, 14(11), 643-647. DOI: 10.1002/bms.1200141113
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U. R. TjadenCenter for Bio-Pharmaceutical Sciences, Division of Analytical Chemistry, PO Box 9502, 2300 RA Leiden, The Netherlands Capillary Gas Chromatography (CGC) is capable of determining underivatized cyclophosphamide (CPA) using SCOT OV 275 columns. Then CPA is subjected to in situ degradation resulting in formation of a cyclization product which can be determined selectively in biological fluids. In routine bioanalysis however cyclization products of CPA metabolites might interfere, e.g. 4-keto CPA. In the present study possible formation of cyclization products of 4-keto CPA similar to CPA was monitored by Mass Spectrometry. Cyclization of 4-keto CPA in siru was demonstrated to occur, resulting in a product similar to that of CPA. Both cyclization products could be determined selectively and it appeared that in situ cyclization of 4-keto CPA was negligible (<5'/0), probably owing to extra stabilization of the CPA metabolite by keto-enol tautomerism as has been demonstrated by NMR.
