Abstract
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.
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