Photocatalytic degradation of selected anticancer drugs and identification of their transformation products in water by liquid chromatography-high resolution mass spectrometry

J Chromatogr A. 2014 Oct 3:1362:135-44. doi: 10.1016/j.chroma.2014.08.035. Epub 2014 Aug 16.

Abstract

A study on the fate of two antineoplastic drugs, methotrexate and doxorubicin, in the aquatic environment is presented. The investigation involved a study of their decomposition under dark experiments, homogeneous photolysis and heterogeneous photocatalysis using titanium dioxide, the identification of intermediate compounds, as well as the assessment of acute toxicity over time. The analysis were carried out using LC (ESI positive mode) coupled with LTQ-Orbitrap analyser; accurate mass-to-charge ratios of parent ions were reported with inaccuracy below 10mmu, which guarantee the correct assignment of their molecular formula in all cases, while their MS(2) and MS(3) spectra showed several structural-diagnostic ions that allowed to characterize the different transformation products and to discriminate the isobaric species. Fourteen and eight main species were identified subsequently to doxorubicin or methotrexate transformation. The major transformation processes for doxorubicin involved (poli)hydroxylation and/or oxidation of the molecule, or the detachment of the sugar moiety. Methotrexate transformation involved decarboxylation or the molecule cleavage. Acute toxicity measurements showed that not only the two drugs exhibit high toxicity, but also their initial transformation products are highly toxic.

Keywords: Doxorubicin; Emerging pollutants; HRMS; Methotrexate; TiO(2); Toxicity.

MeSH terms

  • Aliivibrio fischeri / drug effects
  • Antineoplastic Agents / analysis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Catalysis
  • Chromatography, High Pressure Liquid / methods*
  • Doxorubicin / analysis*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Methotrexate / analysis*
  • Methotrexate / chemistry
  • Methotrexate / pharmacology
  • Photolysis*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tandem Mass Spectrometry / methods*
  • Water / chemistry*

Substances

  • Antineoplastic Agents
  • Water
  • Doxorubicin
  • Methotrexate