Studies on the metabolism of isopnosphamide (NSC-109724) in man

Abstract

A method is described for the quantitative determination of cyclophosphamide, isophosphamide, and trophosphamide and their stable alkylating metabolites on thin-layer chromatography plates with the aid of 4-pyridinealdehydr-2-benzothiazolylhydrazone (PBH). The method requires only 0.01-0.02 ml of urine from patients treated with high doses of cyclophosphamide of isophosphamide, but a careful standarization is required by using reference substances. In the urine of patients treated with isophosphamide, the 4-carboxy derivative and two different dechloroethyl derivatives resulting from side-chain oxidation are the predominant metabolites determined, next to isophosphamide. Side-chain oxidation may be prevalent. Determination of isophosphamide and its stable alkylating metabolites in the urine of 25 patients shows that the ratio of unchanged isophosphamide to its metabolites varies widely. The mean value of the total amount of PBH-reactive compounds exceeded 50% of the given dose, whereas less than 1% was found to be converted to urine metabolites which release acrolein.