Analysis of 4-Demethoxydaunorubicin and Metabolites in Plasma and Urine
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概要
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A high-performance liquid chromatographic procedure, including sample pretreatment, is presented for the analysis of 4-demethoxydaunorubicin, the C_<13> hydroxy metabolite 4-demethoxy-daunorubicinol and four possible aglycone metabolites, 4-demethoxydaunorubicinone, 4-demethoxydaunorubicinolone, 4-demethoxy-7-deoxydaunorubicinone and 4-demethoxy-7-deoxydaunorubicinolone, in plasma and urine samples. Doxorubicin has been utilized as the internal standard of the assay. The sample pretreatment involves liquid-liquid extraction of the buffered (pH 9) biological matrix with chloroform-1-propanol (4 : 1,v/v). Separation of the compounds has been achieved by using a Lichrosorb RP-8 (5 μm) column and by isocratic elution with a mobile phase composed of acetonitrile-phosphate buffer, pH 2.4 (70 : 30,w/w). The flow rate is 1.5 ml/min. Fluorescence detection with excitation at 460 nm and monitoring at 540 nm was applied. The detection limit is 1 ng/ml (using 1.0 ml samples). The applicability of the assay has been demonstrated in a pharmacokinetic study with two rabbits. In plasma, 4-demethoxydaunorubicinol and 4-demethoxydaunorubicinolone were observed as metabolites, whereas 4-demethoxydaunorubicinol was the main metabolite present in urine. Fitting of the plasma concentration versus time curves showed a three-compartment model to give a better description of the plasm concentration-time curves than a two-compartment model.
- 公益社団法人日本薬学会の論文
- 1988-09-25
著者
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BEIJNEN Jos
Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute
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Beijnen J
Netherlands Cancer Inst./antoni Van Leeuwenhoek Huis Amsterdam Nld
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Beijnen Jos
Department Of Clinical Chemistry The Netherlands Cancer Institute
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UNDERBERG Willy
Department of Biomedical Analysis, Faculty of Pharmaceutical Sciences, Utrecht University
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Underberg Willy
Department Of Pharmaceutical Analysis Faculty Of Pharmacy State University Of Utrecht
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Underberg Willy
Department Of Analytical Pharmacy Subfaculty Of Pharmacy State Univeristy Of Utrecht.
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NEEF Cees
Department of Pharmacy, Het Nieuwe Spittaal Hospital
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BOUMA Jaap
Department of Pharmaceutical Analysis, Faculty of Pharmacy, State University of Utrecht
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PAALMAN Adolf
Department of Pharmacy, Slotervaart Hospital
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Neef Cees
Department Of Pharmacy Het Nieuwe Spittaal Hospital
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Bouma Jaap
Department Of Pharmaceutical Analysis Faculty Of Pharmacy State University Of Utrecht
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Paalman Adolf
Department Of Pharmacy Slotervaart Hospital
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