Monitoring the behaviour of 4-ketocyclophosphamideversus cyclophosphamide during capillary gas chromatography by mass spectrometry

Abstract

Document VersionPublisher's PDF, also known as Version of Record (includes final page, issue and volume numbers)Please check the document version of this publication:• A submitted manuscript is the author's version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and page numbers. 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 General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. 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.

Quantitation of anticancer drugs – Cyclophosphamide and ifosfamide in urine and water sewage samples by gas chromatography–mass spectrometry

“…According to previous reports [18,19], CP always gave 2 separated peaks on the chromatogram (Figure 2). The ratios of these 2 peaks were indeed inconsistent causing inaccurate quantitation.…”

“…Twenty μl of the internal standard were added into the sample prior to extraction and derivatization with TFAA. Trifluoroacetic anhydride derivatives of CP (TFA-CP) and IF (TFA-IF) were quantitated in selective ion monitoring (SIM) mode, the mass qualifier ions for TFA-CP were selected at the m/z 212, m/z 150 and m/z 136, with m/z 307 being the quantifier ion; the qualifier ions for and without derivatizations [16][17][18][19] but mostly showed low sensitivity which might be not suitable for preventive purposes. In this presentation, poor chromatographic behaviors of CP and IF have been revealed.…”

Graft copolymerization of methyl acrylate onto nylon1010 initiated by potassium diperiodatonickelate(IV)

“…Therefore GC‐NP detection was established as the method of choice for the fast determination of underivatized CP, IF and their metabolites in human plasma. Unfortunately, it has been demonstrated that thermal decomposition of underivatized CP and IF occurs 27. Therefore, the derivatization of these molecules by trifluoroacetic anhydride is nowadays considered the best approach for analyzing CP, IF and their metabolites by GC 17, 18, 23–26.…”