Separation, characterization, and analysis of epirubicin (4'-epidoxorubicin) and its metabolites from human urine.
Three metabolites of the new antitumor anthracycline epirubicin (4'-epidoxorubicin, 4'-epiDX) detected by HPLC in urine of four patients treated with 75 mg/m2 of the drug, were isolated and identified. In an initial step, fluorescent metabolites present in urine, pooled during the first 24 hr after drug administration, were adsorbed on a column of a styrene divinylbenzene adsorbent. The subsequent gradient elution with aqueous methanol, followed by extraction with 1-butanol at different pH values, allowed separation of 4'-epiDX and its 13-dihydro derivative from the more polar metabolites. Each anthracycline was subsequently separated by reverse phase liquid chromatography, characterized by acid and enzymatic hydrolyses, and studied with chemical-physical analysis. In addition to the parent drug, its 13-dihydro derivative and 4'-O-beta-D-glucuronyl-4'-epiDX which were structurally characterized, a glucuronide conjugate of 13-dihydro-4'-epiDX was identified. In four patients analyzed, approximately 12% of the total administered dose was estimated, by reverse phase HPLC and fluorescence detection, to be excreted in the 0-24-hr pooled urine. 4'-EpiDX accounted for 57% of the total excreted fluorescent anthracyclines, its 4'-O-beta-D-glucuronide for 32%, 13-dihydro-4'-epiDX for 7%, and its glucuronide for 3%, average values.
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004317:Doxorubicin / Q000652:urine*; D004355:Drug Stability; D015251:Epirubicin; D004952:Esters / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D013058:Mass Spectrometry; D008875:Middle Aged; D013056:Spectrophotometry, Ultraviolet
D000903:Antibiotics, Antineoplastic; D004952:Esters; D015251:Epirubicin; D004317:Doxorubicin