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Identification and quantitation of alcophosphamide, a metabolite of cyclophosphamide, in the rat using chemical ionization mass spectrometry

โœ Scribed by Phillip S. Hong; Kenneth K. Chan


Publisher
John Wiley and Sons
Year
1987
Tongue
English
Weight
505 KB
Volume
14
Category
Article
ISSN
1076-5174

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โœฆ Synopsis


Alcophosphamide was identified in urine obtained from Sprague-Dawley rats treated with a 1 : l mixture of cyclophosphamide and f3-(2H4)cyclophosphamide using chemical ionization mass spectrometry and the ion cluster technique. This compound was also quantified in rat plasma using gas chromatographic-mass spectrometry under ammonia chemical ionization following administration of cyclophosphamide. Apparent terminal half life of 76.2 + / -13.7 min and area-under-the concentration-time curve value of 24.8 + / -8.6 p g min/ml were obtained for derived alcophosphamide following iv bolus administration of cyclophosphamide. Following co-administrations of unlabeled and P-('H,)cyclophosphamide via iv/po and iv/ip routes, apparent terminal half-lives of 68.4 + 1-16.4 and 71.8 + 1-10.1 min were found for the iv portions and 106.7+/-25.2 and 73.9+/-5.2 min for the non-iv portions, respectively, for the derived alcophosphamide. Phosphoramide mustard was found to be a major circulating and urinary metabolite in the rat following iv administration of preformed alcophosphamide which gave a plasma half-life of 1.9 h.


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