Blood and tissue concentrations of Bisantrene measured by a simple fluorometric assay

We have developed a simple sensitive fluorometric assay for the measurement of total Bisantrene in plasma, red blood cells, and tissues to facilitate preclinical and clinical pharmacologic assessment of this active anticancer agent. The assay was used to measure the plasma disappearance and tissue concentrations of Bisantrene in the rabbit. Results are comparable to those reported with HPLC assays and with measurement of radioactivity in combusted tissue following IV administration of radiolabeled Bisantrene. We demonstrated that when a plasma concentration of approximately 50 micrograms/ml is not exceeded, Bisantrene remains in solution at that concentration. If Bisantrene is introduced into plasma at a concentration exceeding 50 micrograms/ml, precipitation of the drug is initiated and continues until the plasma concentration is no greater than 15 micrograms/ml. This finding supports our previous recommendation that in clinical trials Bisantrene should be administered at low concentrations over prolonged periods of time to maximize the bioavailability of the drug by minimizing precipitation of the drug in plasma.