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

Abstract

Anthracyclines are a class of pharmaceuticals used in cancer treatment have the potential to negatively impact the environment. To study the possibilities of anthracyclines (represented by pirarubicin and valrubicin) removal, chemical inactivation using NaOH (0.01 M) and NaClO (5%) as decontamination agents and adsorption to powdered nanocrystalline titanium dioxide (TiO2) were compared. The titanium dioxide (TiO2) nanoparticles were prepared via homogeneous precipitation of an aqueous solution of titanium (IV) oxy-sulfate (TiOSO4) at different amount (5-120 g) with urea. The as-prepared TiO2 samples were characterized by XRD, HRSEM and nitrogen physisorption. The adsorption process of anthracycline cytostatics was determined followed by high-performance liquid chromatography coupled with mass spectrometry (LC-MS) and an in-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) technique. It was found that NaClO decomposes anthracyclines to form various transformation products (TPs). No TPs were identified after the reaction of valrubicin with a NaOH solution as well as in the presence of TiO2 nanoparticles. The best degree of removal, 100% of pirarubicin and 85% of valrubicin, has been achieved in a sample with 120 grams of TiOSO4 (TIT120) and TiO2 with 60 grams (TIT60), respectively.

Fig 1. Chemical structures and 3D models of pirarubicin a valrubicin pertaining to the group of anthracycline glycosides.

Fig 2. The porosity of TiO₂ samples. Inset: a hysteresis loop.

Fig 3. The XRD patterns of the titanium samples.

Fig 4. HRSEM image of sample TIT30 prepared by homogeneous precipitation with an initial amount of 30 g TiOSO₄.

Fig 5. HRSEM image of sample TIT100 prepared by homogeneous precipitation with an initial amount of 100 g TiOSO₄.

Fig 6. Scheme of PIRA degradation after its reaction with a solution of 0.01 M NaOH.

Abbreviations: PIRA, pirarubicin; PIRA-TP1-OH, pirarubicinol, PIRA-TP2-OH doxorubicin, PIRA-TP3-OH, doxorubicinol.

Fig 7. Scheme of PIRA degradation after its reaction with a solution of 5% NaClO.

Abbreviations: PIRA, pirarubicin; PIRA-TP1-OCl, doxorubicinon, PIRA-TP2-OCl, 7-deoxydoxorubicinon, PIRA-TP3-OCl, (2R)-2-(1,2-dihydroxyethyl)-2,7-dihydroxy-1,2,3,4,4a,12a-hexahydrotetracene-5,6,11,12-tetraone.

Fig 8. Scheme of VAL degradation after its reaction with a solution of 5% NaClO.

Abbreviations: VAL, valrubicin; VAL-TP1-OCl, N-trifluoroadriamycinol, VAL-TP2-OCl, doxorubicin.

Fig 9. Transformation products formed during the degradation of anthracyclines plotted as a function of the normalized concentration (C/C₀) of pirarubicin and valrubicin decay.

Note: Transformation products formed during the decontamination of pirarubicin in the presence of (a) 5% NaClO agent, (b) 0.01 M NaOH agent; and the decontamination of valrubicin in the presence of 5% NaClO agent (c).

Fig 10

Normalized kinetic curves of pirarubicin (a) and valrubicin (b) adsorption on TiO₂ samples differing in TiOSO₄.

Fig 11. Dependence of k₁ (min^-1) versus surface area (m² g^-1) of prepared TiO₂ samples.

Fig 12

The degree of conversion of pirarubicin (a) and valrubicin (b) using the nanostructured TiO₂-based adsorbents after 120 minutes.

Fig 13. DRIFTS spectra of pirarubicin interaction with the TiO₂ surface (TIT120).

Fig 14. DRIFTS spectra of valrubicin interaction with the TiO₂ surface (TIT60).

Fig 15. The scheme of the adsorption interaction between anthracycline molecules and TiO₂ nanoparticles.