Method for the determination of 4'-deoxydoxorubicin, 4'-deoxydoxorubicinol and their 7-deoxyaglycones in human serum by high-performance liquid chromatography.
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.
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D009279:Naphthacenes; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy
D009279:Naphthacenes; C010012:adriamycin aglycone; C046580:4'-deoxydoxorubicinol 7-deoxyaglycone; D004317:Doxorubicin; C046579:4'-deoxydoxorubicinol; C030851:esorubicin