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Mass spectrometric characterization of activated N ‐(2‐chloroethyl)amido oxazaphosphorine derivatives
Author(s) -
Przybylski M.,
Ringsdorf H.,
Lenssen U.,
Peter G.,
Voelcker G.,
Wagner T.,
Hohorst H. J.
Publication year - 1977
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200040404
Subject(s) - characterization (materials science) , chemistry , radiochemistry , materials science , nanotechnology
The hydroperoxy and several alkylthio derivatives of the antitumor agents cyclophosphamide (2‐bis(2‐chloroethyl)amino tetrahydro‐2 H ‐1,3,2‐oxazaphosphorine 2‐oxide), ifosfamide (3‐(2‐chloroethyl)‐2‐(2‐chloroethylamino) tetrahydro‐2 H ‐1,3,2‐oxazaphosphorine 2‐oxide) and trofosfamide (3‐(2‐chloroethyl)‐2‐ (bis(2‐chloroethyl)amino)tetrahydro‐2 H ‐1,3,2‐oxazaphosphorine 2‐oxide) were characterized by electron impact and field desorption mass spectrometry. The compounds, which are stabilized derivatives of the activated hydroxylated intermediates of cyclophosphamide (ifosfamide, trofosfamide), could be identified as 4‐hydroperoxy and 4‐alkylthio oxazaphosphorines. The existence of diastereomers of these products was demonstrated by thin‐layer chromatography and f.d. mass spectra. Derivatization with benzylmercaptan was found to be an appropriate method for the quantitative isolation and mass spectral identification of the activated metabolic intermediates of cyclophosphamide from biological material. Using this reaction, 4‐hydroxycyclophosphamide and its acyclic tautomer, aldophosphamide, which are too unstable for direct identification, were detected in urine and serum of patients treated with 3 H‐cyclophosphamide.