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Identification of Aldophosphamide as a Metabolite of Cyclophosphamide in Vitro and in Vivo in Humans¹

Department of Pharmacology and Experimental Therapeutics [C. F., M-N. K., S. S.] and Oncology Center [M. C.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and Collaborative Research, Inc., Waltham, Massachusetts 02154 [A. M., O. M. F.]

Aldophosphamide (NSC 254), a putative key metabolite of cyclophosphamide, has now been isolated as a cyanohydrin derivative from an incubation mixture of cyclophosphamide with mouse liver microsomes in vitro and from the plasma of a cyclophosphamide-treated patient. The cyanohydrin has been shown to be identical with an authentic synthetic sample by mass spectrometry and combined gas chromatography-mass spectrometry.

¹ This work was supported by Grants GM-21204 and CA-16783 from the USPHS and by National Cancer Institute Contract NO1-GM-60506.

² Recipient of USPHS Research Career Development Award GM-70417.

³ Recipient of USPHS, MARC Fellowship GM-05709. On leave from Lincoln University, Lincoln, Pa.

⁴ Recipient of USPHS Research Career Development Award CA-00103.

Received 2/14/77. Accepted 4/29/77.