DETERMINATION OF 4-HYDROXYIFOSFAMIDE IN BIOLOGICAL MATRICES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

A high-performance liquid chromatographic method has been developed fo r the determination of 4-hydroxyifosfamide, a metabolite of ifosfamide , in plasma of cancer patients. The analyte is derivatized to 7-hydrox yquinoline, which can be detached fluorimetrically. The calibration gr aph is linear in the concentration range 0.05-25 mu M, the limit of de tection being 40 nM. Any inference from acrolein, another metabolite o f ifosfamide, was ruled out. 4-Hydroxyifosfamide is very unstable in p lasma and a stabilization procedure by adding citric acid has been dev eloped. Thus treated, the samples were stable for 4 days. Analysis of a patient's plasma samples revealed that the 6-hydroxifosfamide concen tration did not exceed 10 mu M. (C) 1997 Elsevier Science B.V.