HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS OF THE CARDIOPROTECTIVE AGENT DEXRAZOXANE IN HUMAN PLASMA AND URINE

For the purpose of a pharmacokinetic study in the comparison of two in travenous pharmaceutical formulations of the cardioprotective agent de xrazoxane, we have developed an High Performance Liquid Chromatographi c (HPLC) assay to quantify the drug in human plasma and urine. The pla sma sample pretreatment involved a protein precipitation step with ace tonitrile followed by an extraction with 10% 2-methyl-2-propanol in ch loroform (v/v). Urine samples were diluted in distilled water and subs equently extracted with 10% 2-methyl-2-propanol in chloroform (v/v). A fter evaporation of the organic solvents, the residues were dissolved and analysed on a mu Bondapak Phenyl column with a mobile phase consis ting of 0.01 M potassium phosphate pH 4.7 and methanol (8:2, v/v). Det ection was performed at 208 nm. The lower limit of quantitation was 0. 1 mu g/mL and 10 mu g/mL for plasma and mine respectively, using 1.0 m L sample volumes. The usefulness of the method has been demonstrated i n clinical samples originating from patients treated with dexrazoxane. Dexrazoxane is not stable in plasma at ambient temperature: after 6.5 hours the initial concentration was 42.6 +/- 1.0% (n=3) of the origin al concentration of 100 mu g/mL. After sampling in the clinic, plasma samples should be stored immediately at -30 degrees C. Under these con ditions dexrazoxane is stable for at least 5 months. In urine the drug is stable for 24 hours when stored at 4-8 degrees C. An aliquot of th e voided urine sample can be stored at -30 degrees C for at least 4 mo nths without drug decomposition.