Article pubs.acs.org/ac
Electrochemical Study of the Anticancer Drug Daunorubicin at a Water/Oil Interface: Drug Lipophilicity and Quantification José A. Ribeiro, F. Silva, and Carlos M. Pereira* Faculdade de Ciências da Universidade do Porto, Departamento de Química e Bioquímica, Centro de Investigaçaõ em Química, Linha 4, Rua do Campo Alegre 687, 4169-007 Porto, Portugal ABSTRACT: In this work, the ion transfer mechanism of the anticancer drug daunorubicin (DNR) at a liquid/liquid interface has been studied for the first time. This study was carried out using electrochemical techniques, namely cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The lipophilicity of DNR was investigated at the water/1,6dichlorohexane (DCH) interface, and the results obtained were presented in the form of an ionic partition diagram. The partition coefficients of both neutral and ionic forms of the drug were determined. The analytical parameter for the detection of DNR was also investigated in this work. An electrochemical DNR sensor is proposed by means of simple ion transfer at the water/DCH interface, using DPV as the quantification technique. Experimental conditions for the analytical determination of DNR were established, and a detection limit of 0.80 μM was obtained. chromatography (HPLC) method with fluorescence detection and using solid-phase extraction (SPE) for the separation of liposomal and free DNR from the plasma of patients treated with Daunoxome, which is a liposomal formulation of DNR. Some other methods have been published for the determination of DNR, doxorubicin (DXR), idarubicin (IDA), and epirubicin (EPI), as well as their rubicinol metabolites in biological fluids by HPLC, and these have been detected by fluorescence13 and mass spectrometry.14 In the method developed by Hempel et al.,15,16 the total plasma DNR concentrations were measured, after SPE or liquid/liquid extraction, with capillary electrophoresis and laser-induced fluorescence (LIF) detection. This technique was also used by Perez-Ruiz and co-workers17 to separate DRN, DXR, and IDA in serum samples, and the same technique was used by Siméon and co-workers18 in the determination of the content of DNR in biopsies and plasmas from patients having a Kaposi sarcoma. Finally, Chen et al.19 have developed a resonance light scattering (RLS) quenching assay for the sensitive determination of DXR and DNR. Over the last three decades, ion transfer voltammetry at an interface between two immiscible electrolyte solutions (ITIES) has been extensively used to study the transfer of many inorganic and organic ions.20 Interfacial transfers of several biologically relevant species, including neurotransmitters,21−24 aminoacids,25,26 peptides27,28 and proteins,29−31 carbohydrates,32,33 food additives,34 ionic drugs,35,36 and DNA37,38
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aunorubicin (DNR), which is also known as daunomycin, is an anthracycline-derived antibiotic that was first isolated from a unique strain of Streptomyces. It consists of a weakly basic amino sugar, daunosamine, linked via a glycosidic bond to the red-pigmented tetracyclic moiety daunomycinone.1 This four-ring structure is the chromophore of the anthracycline molecule, and aqueous solutions of DNR are red. The anthraquinone ring also has the ability to intercalate between DNA base pairs.2,3 Clinically, DNR possesses high antitumor activity and is used primarily in the treatment of acute leukemias.4 However, DNR produces a potentially fatal cardiotoxicity that is dependent on the total cumulative dose administered.5 Consequently, highly sensitive analytical methods are essential for the evaluation and administration of this drug.6 From a biological point of view, the amino sugar is most important and the pKa value of the amino group is ∼8.7 In aqueous solution at pH
