This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bryant, B. M. Articles by Smyth, J. F. Search for Related Content PubMed PubMed Citation Articles by Bryant, B. M. Articles by Smyth, J. F.

Quantification by Gas Chromatography of N,N'-Di-(2-chloroethyl)-phosphorodiamidic Acid in the Plasma of Patients Receiving Isophosphamide^{1, 2,}

Institute of Cancer Research, Downs Road, Sutton, Surrey, SM2 5PX, England [B. M. B., M. J., M. H. B., I. E. S.], and The University of Edinburgh, Medical Oncology Unit, The Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland [J. F. S.]

A sensitive method, based on gas chromatography using a phosphorus-specific flame photometric detector, has been developed for quantifying N,N'-di-(2-chloroethyl)phosphorodiamidic acid (isophosphoramide mustard), the putative active metabolite of isophosphamide, in human plasma. Phosphoramide mustard was used as internal standard, and the two compounds were converted into separable trimethyl derivatives by reaction with methyl iodide in the presence of silver oxide. The chemistry of the derivatization process has been elucidated using gas chromatography-electron impact mass spectrometry and selected ion monitoring. Levels of isophosphamide and of isophosphoramide mustard were measured in the plasma of patients receiving isophosphamide (2 g/sq m). Peak plasma levels of isophosphoramide mustard of 18.6 to 30.3 nmol/ml occurred at 2 to 4 hr, and levels were still appreciable (6.3 to 11.3 nmol/ml) at 24 hr.

¹ This investigation was supported by a grant to the Institute of Cancer Research from the Medical Research Council (Grant G973/786).

² 2-(2-Chloroethyl)amino-3-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide.

³ Gordon Hamilton Fairley Research Training Fellow.

⁴ To whom requests for reprints should be addressed.

Received 3/18/80. Accepted 8/27/80.