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Quantitation by Gas Chromatography-Chemical Ionization Mass Spectrometry of Cyclophosphamide, Phosphoramide Mustard, and Nornitrogen Mustard in the Plasma and Urine of Patients Receiving Cyclophosphamide Therapy¹

Department of Pharmacology and Experimental Therapeutics [I. J., C. F., M. A., M-N. K.] and Oncology Center [R. B. B., M. C.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Unambiguous and sensitive methods based on gas chromatography-chemical ionization mass spectrometry have been developed to quantitate cyclophosphamide and two alkylating and cytotoxic metabolites, phosphoramide mustard and nornitrogen mustard. The levels of these materials have been determined in the plasma and urine of five patients receiving cyclophosphamide, 60 or 75 mg/kg i.v. Park plasma levels of phosphoramide mustard of 50 to 100 nmoles/ml were found at 3 hr after cyclophosphamide administration. Variable levels of nornitrogen mustard were found in the plasma. This product may be arising in part from the decomposition of other metabolites during sample storage and preparation.

¹ This research was supported by USPHS NIH Grants CA-16783 and GM-21248 and by grants from the Andrew Mellon Fund and the American Cancer Society, Maryland Division.

² Present address: Department of Medicinal Chemistry and Pharmacognosy, Purdue University School of Pharmacy and Pharmacal Sciences, West Lafayette, Ind. 47907.

³ Recipient of USPHS Research Career Development Award CA-00103.

⁴ Recipient of USPHS Research Career Development Award GM-70417.

Received 5/27/77. Accepted 11/10/77.

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