Anthracycline antibiotics derivate mitoxantrone—Destructive sorption and photocatalytic degradation

Abstract

Nanostructured titanium(IV) oxide was used for the destructive adsorption and photocatalytic degradation of mitoxantrone (MTX), a cytostatic drug from the group of anthracycline antibiotics. During adsorption on a titania dioxide surface, four degradation products of MTX, mitoxantrone dicarboxylic acid, 1,4-dihydroxy-5-((2-((2-hydroxyethyl)amino)ethyl)amino)-8-((2-(methylamino)ethyl)amino)anthracene-9,10-dione, 1,4-dihydroxy-5,8-diiminoanthracene-9,10(5H,8H)-dione and 1,4-dihydroxy-5-imino-8-(methyleneamino)anthracene-9,10(5H,8H)-dione, were identified. In the case of photocatalytic degradation, only one degradation product after 15 min at m/z 472 was identified. This degradation product corresponded to mitoxantrone dicarboxylic acid, and complete mineralization was attained in one hour. Destructive adsorbent manganese(IV) oxide, MnO2, was used only for the destructive adsorption of MTX. Destructive adsorption occurred only for one degradation product, mitoxantrone dicarboxylic acid, against anatase TiO2.

Investigating the interaction of mitoxantrone with anionic surfactants by spectrofluorimetry and its application for the feasible analysis of pharmaceutical preparation and biological fluids

“…Degradation probably proceeded through protonation of secondary amino groups linking aliphatic side chains with anthracenedione moieties, followed by the removal of these two side chains as N ‐ethyl aminoethanol (CH 2 CH 2 NHCH 2 CH 2 OH) (Figure 6). This aliphatic side chain fracture is thought to induce a delocalization of the free nitrogen electron pairs, which provide electron rotation and stability to the molecule, [ 40 ] therefore their removal resulted in relocation of the nitrogen electron pair. The primary amine group would be protonated in the acidic medium (pH 3.0) and therefore the electron pair would no longer be available, leading to a decrease in intrinsic fluorescence of the resulting product.…”

Removal of anthracycline cytostatics from aquatic environment: Comparison of nanocrystalline titanium dioxide and decontamination agents

“…The procedure for testing the degradation of cytostatics on the surface of reactive sorbents is based on previously published works [23,31,32].…”

“…Then, the solution was analyzed immediately by HPLC to determine the oxidation or hydrolysis of the transformation products. A similar assay was used to test the degradation of cytostatics on the surface of nanostructured titanium dioxides [33]. In this case, the initial concentration of the cytostatic drug stock solution was 2 mg·mL -1 , as recommended by the drug manufacturer.…”

“…Recently, we have dealt with a detailed study of the degradation of cytostatics pertaining to the class of anthracycline derivatives (doxorubicin and epirubicin) [23], anthraquinone derivates (mitoxantrone) [24] and nitrogen mustards family (cyclophosphamide and ifosfamide) [25] in decontamination agents (NaOH, NaClO) and on the surface of nanostructured adsorbents (TiO 2 , MnO 2 ).…”

H2O2-assisted photoelectrocatalytic degradation of Mitoxantrone using CuO nanostructured films: Identification of by-products and toxicity

“…These proposed structures were based on our knowledge of the degradation of pharmaceuticals and other organic compounds, and based upon study of the published data (Machulek et al 2009;Daghrir et al 2013b;Cavalcante et al 2015;Gómez-Canela et al 2015;Štenglová-Netíková et al 2018). These intermediates are largey unreported in the literature, except the compound with m/z 443 which has already been identified as a metabolic (Rossato et al 2013).…”