Electrochemical oxidation of mitoxantrone at a glassy carbon electrode A.M. Oliveira Brett a,* , T.R.A. Macedo b , D. Raimundo b , M.H. Marques b , S.H.P. Serrano c a Departamento de Quõ Âmica, Faculdade de Cie Ãncias e Tecnologia, Universidade de Coimbra, 3000 Coimbra, Portugal b Faculdade de Medicina, Universidade de Coimbra, 3000 Coimbra, Portugal c Instituto de Quõ Âmica, Universidade de S. Paulo, CP 26077, 05599-970 S. Paulo, Brazil Received 28 July 1998; received in revised form 3 November 1998; accepted 8 November 1998 Abstract Mitoxantrone is an anthracycline used as an antitumour antibiotic for leukaemia and breast cancer treatment, due to its interaction with DNA. However, the molecular mechanism of the antitumour action is not completely understood. Using a glassy carbon electrode the electrochemical oxidation of mitoxantrone was shown to be a complex, pH-dependent, irreversible electrode process involving several metabolites. Comparison of the electrochemical oxidation behaviour of mitoxantrone, ametantrone and aminantrone enabled a deeper understanding of the mechanism and showed the relevance of electrochemical data for the understanding of the cytotoxicity of mitoxantrone. Since mitoxantrone and its oxidation products adsorb strongly on the electrode surface, causing severe problems of electrode fouling, reproducible electroanalytical determinations could only be done at very low concentrations and in an aqueous buffer supporting electrolyte containing 30% ethanol. The detection limit obtained was 10 7 M. # 1999 Elsevier Science B.V. All rights reserved. Keywords: Bioelectrochemistry; Mitoxantrone oxidation; Voltammetry 1. Introduction Mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2-hydro- xyethyl)amino]ethyl]amino]-9,10-anthracenedione) (MTX) is an aminoanthraquinone, an anthracycline antibiotic, used as an antitumour antibiotic, due to its interaction with DNA [1]. It has a planar heterocyclic ring structure, the positively charged, nitrogen-con- taining side chains projecting out from the molecule, which stabilize the ring in between base pairs by intercalating with the negatively charged phosphate backbone of DNA [2,3]. Originally synthesized as stable dyes [3±5], anthracenediones are used as anti- tumour antibiotics for leukaemia and breast cancer treatment. MTX has been shown to induce condensa- tion of nucleic acids but the most dominant molecular mechanism of antitumour action appears to be the induction of long-term DNA damage. Cytotoxic effects, although less than for other anticancer drugs, cause myelosuppression, cardiac toxicity and muco- sitis as well as other common effects. The mechanism of action of MTX is not completely understood but studies with an electrochemical DNA-biosensor [6], enabled the observation of DNA damage occurring with time which suggests that MTX intercalates with DNA and slowly interacts with it causing some break- ing of the hydrogen bonds. Analytica Chimica Acta 385 (1999) 401±408 *Corresponding author. Tel.: +351-39-835295; fax: +351-39- 835295; e-mail: brett@cygnus.ci.uc.pt 0003-2670/99/$ ± see front matter # 1999 Elsevier Science B.V. All rights reserved. PII: S0003-2670(98)00807-1