7-deoxy-13-dihydroadriamycinone and adriamycinol

To investigate the diffusion and accumulation of doxorubicin metabolites in the ascites of patients with ovarian cancer following intravenous injection, as a model for intraperitoneal accumulation of drugs.. The concentrations of doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high-performance liquid chromatography in the serum and in the ascites of seven patients with recurrent ovarian carcinoma suffering from symptomatic ascites and treated with intravenous doxorubicin.. Doxorubicin metabolites accumulated in the peritoneal cavity. The concentrations of the doxorubicin metabolites were initially higher in the serum compared to the ascitic fluid, but following several hours the doxorubicin metabolites became higher in the ascites, and remained detectable in the ascites for up to 168h, long after disappearance from the serum.. Doxorubicin metabolites accumulate in the ascites and are cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Ascites; Chromatography, High Pressure Liquid; Disease Progression; Doxorubicin; Female; Humans; Middle Aged; Naphthacenes; Ovarian Neoplasms; Paracentesis; Prognosis

A sensitive and selective reversed-phase high-performance liquid chromatographic method for the quantification of doxorubicin and its metabolites doxorubicinol, 7-deoxydoxorubicinone and 7-deoxydoxorubicinolone was developed and validated for a variety of murine specimens. Daunorubicin was used as internal standard. Sample pretreatment involved liquid-liquid extraction of 200 microl sample with 1 ml of chloroform-1-propanol (4:1, v/v). Chromatographic separation was achieved isocratically on a LiChrosorb RP-8 analytical column at ambient temperature. The mobile phase consisted of acidified water (pH 2.05)-acetonitrile-tetrahydrofuran (80:30:1, v/v/v). The column effluent was monitored fluorimetrically at an excitation wavelength of 460 nm and an emission wavelength of 550 nm. The lower limits of quantitation were in the range 1.8-2.4 nM. Spiked murine specimens and samples from treated mice were subjected to stability studies. The results demonstrated the importance of validation in all relevant specimens, since the accuracy and precision were highly matrix-dependent. Accuracies and precisions of measured drug concentrations in liver, spleen, muscle, gastrointestinal tissues, diluted bile, feces and urine were lower than in the other matrices. Doxorubicin was unstable in diluted bile, but not in the other specimens. The method is suitable for studying the pharmacokinetics of doxorubicin and its metabolites in mice.

Topics: Animals; Antibiotics, Antineoplastic; Bile; Chromatography, High Pressure Liquid; Doxorubicin; Feces; Female; Humans; Male; Mice; Naphthacenes; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution