Improved high-performance liquid chromatography of the new antineoplastic agents bisantrene and mitoxantrone

Yei Mei Peng, Debra Ormberg, David S. Alberts, Thomas P. Davis

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

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 prologned 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°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°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.

Original languageEnglish (US)
Pages (from-to)235-247
Number of pages13
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume233
Issue number1
DOIs
StatePublished - Dec 10 1982

ASJC Scopus subject areas

  • Chemistry(all)

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