Micellar electrokinetic capillary chromatography reveals differences in intracellular metabolism between liposomal and free doxorubicin treatment of human leukemia cells

Doxil® is a pegylated liposome formulation of the anthracycline doxorubicin. To better explain observed differences in the toxicity of Doxil® and free doxorubicin in solution, the intracellular metabolism of the formulations after treatment in CCRF-CEM and CEM/C2 human leukemia cell lines was investigated. Using micellar electrokinetic capillary chromatography with laser-induced fluorescence detection, with a 63 zepto (10−21) mole doxorubicin limit of detection, five common metabolites and doxorubicin were detected upon treatment with both of these drug delivery systems. Two unique metabolites appeared with the Doxil® and two unique metabolites appeared with the free doxorubicin delivery systems. For common metabolites, the relative amount of metabolite generated from Doxil® was approximately 10 times higher than for free doxorubicin.