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

Abstract

Alcophosphamide was identified in urine obtained from Sprague-Dawley rats treated with a 1:1 mixture of cyclophosphamide and beta-(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 micrograms min/ml were obtained for derived alcophosphamide following iv bolus administration of cyclophosphamide. Following co-administrations of unlabeled and beta-(2H4)cyclophosphamide via iv/po and iv/ip routes, apparent terminal half-lives of 68.4 +/- 16.4 and 71.8 +/- 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.