SIMULTANEOUS DETERMINATION OF EPIRUBICIN, DOXORUBICIN AND THEIR PRINCIPAL METABOLITES IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND ELECTROCHEMICAL DETECTION

A high-performance liquid chromatographic method with electrochemical detection has been developed for the simultaneous determination of epi rubicin. 13-S-dihydroepirubicin, doxorubicin and 13-S-dihydrodoxorubic in in human plasma. An aliquot of 200 mu l plasma, spiked with interna l standard, was extracted by solid-phase extraction using polymeric ad sorbent columns. Chromatography was performed using a C-18 reversed-ph ase column with a mobile phase consisting of water-acetonitrile (71:29 , v/v) containing 0.05 M Na2HPO4 and 0.05% v/v triethylamine adjusted to pH 4.6 with citric acid. Linearity of the method was obtained in th e concentration range of 1-500 ng/ml for all the analytes. Analytical recoveries of the analytes ranged fr om 89 to 93%. The assay con be us ed for the simultaneous determination of the four analytes, or for epi rubicin and its metabolite or doxorubicin and its metabolite, using th e other parent drug as an internal standard. The method was applied to analyze human plasma samples from patients treated with epirubicin us ing doxorubicin as an internal standard. (C) 1998 Elsevier Science B.V .