Improved high-performance liquid chromatography of the new antineoplastic agents bisantrene and mitoxantrone.
Bisantrene and mitoxantrone are two new anthracene derivatives which have shown significant antitumor activity against a wide variety of animal tumors and in human phase I and II clinical trials. We have developed a rapid, simple and sensitive sample cleanup procedure and high-performance liquid chromatographic (HPLC) assay for both drugs. This method uses a commercially available mini-cartridge with C18 reversed-phase packing to isolate the drugs from the biological matrix prior to HPLC. For both drugs the average recovery of the assay was 98 +/- 6% with a coefficient of variation (C.V.) of less than 7%. Using this new method our assay sensitivity has improved to less than 10 ng/ml for bisantrene and 1 ng/ml for mitoxantrone, allowing us to document a prolonged terminal phase plasma half-life for both bisantrene and mitoxantrone. Equilibrium dialysis studies showed that both drugs are highly protein bound. Mitoxantrone appears less stable in human plasma than bisantrene. Recoveries from plasma after a 24-h incubation at 25 and 37 degrees C were 40 and 20% for mitoxantrone and 90 and 85% for bisantrene, respectively. Addition of ascorbic acid prior to incubation of mitoxantrone in human plasma at 37 degrees C resulted in less than a 10% decrease in the latter's concentration over a 24-h period. To maintain sample integrity, all plasma samples should be fortified with ascorbic acid and kept frozen prior to analyses.
D000880:Anthraquinones / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003956:Dialysis; D006207:Half-Life; D006801:Humans; D013058:Mass Spectrometry; D008942:Mitoxantrone; D013696:Temperature; D013997:Time Factors
D000880:Anthraquinones; D000970:Antineoplastic Agents; D001798:Blood Proteins; D008942:Mitoxantrone