ISSN:
1052-9306
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The antitumour agent cyclophosphamide - {2-[bis(2-chloroethyl)amino]-tetrahydro-2H -1,3,2-oxaza-phosphorine 2-oxide} - is chiral owing to asymmetry at phosphorus. The differential metabolism of the enantiomers [(+)-cyclophosphamide and (-)-cyclophosphamide] can be monitored by mass spectrometry if pseudoracemates consisting of either unlabelled [2H0] (+)- and tetradeuterated [2H4] (-)-cyclophosphamide or of [2H0](-) and [2H4](+) enantiomers are administered. Using this principle, methodology has been developed for determining the enantiomer ratios of cyclophosphamide and two metabolites, 4-ketocyclophosphamide {2-[bis(2-chloroethyl)amino] tetrahydro-2H-1,3,2-oxazaphosphorin-4-one 2-oxide} and carboxyphosphamide [2-carboxyethyl N,N-bis(2-chloroethyl)phosphorodiamidate] recovered from the urine of mice. The drug and the two metabolites were quantified using [2H10]cyclophosphamide, 4-keto-[2H8]cyclophosphamide and [2H6]carboxyphosphamide respectively, as internal standards. The amount of cyclophosphamide excreted was small and neither enantiomer preponderated markedly, but the minor metabolite, 4-ketocyclophosphamide, was markedly depleted in the enantiomer derived from (-)-cyclophosphamide, whereas the major metabolite, carboxyphosphamide, was slightly depleted in the enantiomer derived from (+)-cyclophosphamide.
Additional Material:
2 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bms.1200040609
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