Transformation of tamoxifen and its major metabolites during water chlorination: Identification and in silico toxicity assessment of their disinfection byproducts

Water Res. 2015 Nov 15;85:199-207. doi: 10.1016/j.watres.2015.08.036. Epub 2015 Aug 20.

Abstract

The selective estrogen receptor modulator tamoxifen is the most commonly used drug for the treatment and prevention of breast cancer. Tamoxifen is considered as a pro-drug since it is known to exert its pharmacological effect through its major active metabolites, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen, which are mainly excreted in the urine in the days following administration. In the present work, the reactivity of tamoxifen and its major active metabolites in free chlorine-containing water was investigated for the first time. Under the studied chlorination conditions, tamoxifen was fairly stable whereas its metabolites were quickly degraded. A total of thirteen chlorinated byproducts were tentatively identified by ultra-high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. Time-course profiles of the identified byproducts were followed in real wastewater samples under conditions that simulate wastewater disinfection. A preliminary assessment of their acute aquatic toxicity at two trophic levels by means of quantitative structure-activity relationship models showed that the identified byproducts were up to 110-fold more toxic than the parent compounds.

Keywords: Chlorine; Cytostatic drugs; Orbitrap; Reactivity; Tamoxifen; Transformation products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Disinfection
  • Halogenation
  • Quantitative Structure-Activity Relationship
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / analysis
  • Tamoxifen / chemistry
  • Tamoxifen / toxicity*
  • Tandem Mass Spectrometry
  • Water Pollutants, Chemical / analysis
  • Water Pollutants, Chemical / chemistry
  • Water Pollutants, Chemical / toxicity*
  • Water Purification*

Substances

  • Water Pollutants, Chemical
  • Tamoxifen
  • afimoxifene
  • 4-hydroxy-N-desmethyltamoxifen