Determination of doxorubicin and doxorubicin-3-ol in rat heart.

The discovery of a delayed form of DXR-induced cardiotoxicity raises the question whether the presence of the drug or of metabolites in myocardial cells is necessary for the development of cardiotoxicity. The present investigations deal with a new method for the determination of DXR and of its main metabolite, DXR-3-ol, in cardiac cells. Rat hearts "ex-vivo", isolated 24 h after i.v. administration of 6 mg/kg DXR and 20 micro C of DXR-14C, were perfused with ice-cold Tyrode solution, which releases anthracyclines from extracellular spaces. After homogenization DXR and DXR-3-ol were extracted from the cell at room temperature. The separation was carried out by HPLC; the recovery was about 95%, measured by the extracted radioactivity compared with that of the pellet residue