DETERMINATION OF PLASMA-CONCENTRATIONS OF EPIRUBICIN AND ITS METABOLITES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY DURING A 96-H INFUSION IN CANCER-CHEMOTHERAPY

In order to determine epirubicin and its metabolites at low concentrat ions (<38 ng/ml) in small plasma samples, a fast reliable method based on a precipitation pre-treatment and sensitive reversed-phase isocrat ic HPLC has been developed and validated for epirubicin in the range 5 -100 ng/ml. The R.S.D. was 5-9% over this concentration range. For hum an serum containing 25 ng/ml of epirubicin, the inter- and intra-day v ariation was <10%. Recoveries of the metabolites epirubicinol, 7-deoxy doxorubicinone and 7-deoxydoxorubicinolone at 20 ng/ml ranged from 94- 104%. The assay has been used to study human plasma samples taken duri ng a 96-h infusion of epirubicin in a patient with multiple myeloma. T he combined levels of the unseparated metabolites, epirubicin glucuron ide and epirubicinol glucuronide, were semiquantitatively determined a fter treatment with beta-glucuronidase. The metabolites epirubicinol a nd 7-deoxydoxorubicinolone, but not 7-deoxydoxorubicinone, were also d etected and measured.