adriamycin-aglycone and Neoplasms

A rapid sensitive and selective method is developed for the plasma analysis of doxorubicin and its metabolites, doxorubicinol and doxorubicinone with daunorubicin as the internal standard, by using high performance liquid chromatography (HPLC) with fluorescence detection and a "zorbax ODS" column. An eluent containing tetrahydrofuran and trietylamine afforded improved efficiency and resolution and was used to resolve the four anthracycline derivatives in a sole isocratic run. An example of the plasma levels obtained in a cancerous patient after two different administrations is shown.

Topics: Chromatography, High Pressure Liquid; Daunorubicin; Doxorubicin; Humans; Naphthacenes; Neoplasms; Reference Values

4'-Deoxydoxorubicin (4'-DOX) is a new and structurally similar analogue of the anti-cancer drug adriamycin (ADR). Based on known pathways of metabolism of ADR a high-performance liquid chromatographic method for the separation and identification of 4'-DOX and five possible metabolites was developed. Sensitivity for serum is 10 ng/ml for 4'-DOX and its alcoholic product 4'-deoxydoxorubicinol (4'-DOL) and 2 ng/ml for four of its aglycone products with coefficients of variation in k' of less than 5% throughout the day. An extraction step with better than 80% recovery of 4'-DOX and five reference metabolites from serum is described. Analysis of patient sera identified two metabolite peaks. These co-eluted with the reference metabolites of 4'-DOL and the 7-deoxyaglycone of 4'-DOX. Pharmacokinetics of the parent drug followed a two-compartment model. Both the metabolites were produced quickly and disappeared quickly.

Topics: Biotransformation; Chromatography, High Pressure Liquid; Doxorubicin; Humans; Kinetics; Naphthacenes; Neoplasms