par Dubois, Jacques ;Hanocq, Michel ;Atassi, Ghanem
Référence International journal of pharmaceutics, 35, page (219-226)
Publication Publié, 1987
Article révisé par les pairs
Résumé : Daunorubicin (DNR) is an anthracycline glycoside antibiotic widely used in the treatment of malignant diseases. Quantitative determination of low levels of this drug has been often studied in plasma. In this work an original assay was developed to determine DNR and its main metabolites (daunorubicinol and daunorubicinone) in solid tumors (b16melanoma and p388 leukemia) which were inoculated (s.c. route) to C57 B1/6 and CDF1 mice. Several procedures were investigated to extract antracyclines from tissues but the quantitative extraction of these drugs needs the following main steps: (1) release of antineoplastic molecules from binding to DNA and RNA by Ag+; (2) breaking of drug-protein binds and desorption of the adsorbed compounds on the complex tissular matrices; (3) purification of the tissue extract by adsorption on a C18 Bond Elut column. The mixture of anthracyclines was then separated by high-performance liquid chromatography (HPLC) using a C18 Merck Lichrocart column (6.5 μm; length, 250 mm: diameter, 4 mm) and the mobile phase consisted of a CH3CN-NaH2PO4 0.05 M-THF (27.5:71.5:1) mixture. The DNR derivatives are ideally suited to electrochemical detection (LCEC), and the use of LCEC with the extraction procedure described, allows the determination of quantities of anthracycline as small as 1 ng/g of tumor. © 1987.