New method for the determination of doxorubicin, 4'-epidoxorubicin and all known metabolites in cardiac tissue.
4'-Epidoxorubicin, doxorubicin (internal standard) and eight metabolites were extracted from heart tissue homogenate by a mixture of tetrahydrofuran-water (1:2, v/v) and purified by C18 Sep-Pak cartridges. The buffer used to prepare the homogenate contained glucaric acid-1,4-lactone and glucose, to prevent decomposition of the 4'-epidoxorubicin glucuronides. Anthracyclines were separated by high-performance liquid chromatography within 14 min and detected by fluorescence. Recoveries ranged from 49 to 75%. The detection limits of the individual anthracyclines ranged from 0.5.10(-11) to 2.5.10(-11) mol/g wet weight. The peak-height ratios of the fluorescence intensities of the anthracyclines versus doxorubicin were linear from 2.5.10(-11) to 250.10(-11) mol/g wet weight. Within- and between-day precisions of the assay varied between the anthracyclines and were in the ranges 3-12% (n = 6) and 2-11% (n = 6), respectively.
Maessen
P A
PA
Department of Oncology, Academic Hospital Free University, Amsterdam, The Netherlands.
Pinedo
H M
HM
Mross
K B
KB
van der Vijgh
W J
WJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000032:analysis*; D015251:Epirubicin; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009206:Myocardium / Q000032:analysis*
D015251:Epirubicin; D004317:Doxorubicin