QUANTIFICATION BY GAS-CHROMATOGRAPHY OF N,N'-DI-(2-CHLOROETHYL)-PHOSPHORODIAMIDIC ACID IN THE PLASMA OF PATIENTS RECEIVING ISOPHOSPHAMIDE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (12) , 4734-4738
Abstract
A sensitive method, based on gas chromatography using a P-specific flame photometric detector, was developed for quantifying N,N''-di-(2-chloroethyl)phosphorodiamidic acid (isophosphoramide mustard); the putative active metabolite of [the antineoplastic drug] isophosphamide, in human plasma. Phosphoramide mustard was used as internal standard; the 2 compounds were converted into separable trimethyl derivatives by reaction with methyl iodide in the presence of silver oxide. The chemistry of the derivatization process was 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/m2). Peak plasma levels of isophosphoramide mustard of 18.6-30.3 nmol/ml occurred at 2-4 h; levels were still appreciable (6.3-11.3 nmol/ml) at 24 h.