TY - JOUR

T1 - Monitoring of methotrexate chlorination in water

AU - Roig, Benoit

AU - Marquenet, Baptiste

AU - Delpla, Ianis

AU - Bessonneau, Vincent

AU - Sellier, Amélie

AU - Leder, C

AU - Thomas, Olivier

AU - Bolek, R

AU - Kummerer, K

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/6/15

Y1 - 2014/6/15

N2 - Anti-cancer drugs are an important class of pharmaceutical products. Methotrexate (MTX) is a folic acid antagonist used in high doses as antimetabolite in anti-cancer treatment as well as in low doses for the treatment of rheumatoid arthritis and adults' psoriasis. In the past, several anti-cancer drugs, including methotrexate, have been found in the environment. Their presence in water, especially if used for the production of drinking water, is even in low concentrations of particular interest, due to the risk to retrieve them in the consumed water and their high activity and grave effects. But prior to usage as drinking water, raw waters are treated and chlorination is a common practice in several countries. As such a treatment can lead to the formation of organochlorine in water, the study of the fate of MTX during chlorination in a batch trial was carried out. The reaction was monitored by dissolved organic carbon (DOC) and by fluorescence and UV spectroscopy. Investigation of by-products formed was done with liquid chromatography/mass spectrometry (LC/MS). Under the given experimental conditions, Methotrexate was eliminated rapidly (t1/2 around 21 min). However, DOC elimination was incomplete. Monitoring with LC-MS showed the formation of a monochlorinated transformation product of MTX. In silico analysis of the proposed transformation products for different carcinogenic, mutagenic and genotoxic endpoints with different software platforms provided no clear evidence that the possible transformation products after chlorination might be more toxic than the parent compound. However, since a number of alerts is altered after chlorination, it cannot be excluded that the toxicity of these transformation products might be modulated compared with the parent compound.

AB - Anti-cancer drugs are an important class of pharmaceutical products. Methotrexate (MTX) is a folic acid antagonist used in high doses as antimetabolite in anti-cancer treatment as well as in low doses for the treatment of rheumatoid arthritis and adults' psoriasis. In the past, several anti-cancer drugs, including methotrexate, have been found in the environment. Their presence in water, especially if used for the production of drinking water, is even in low concentrations of particular interest, due to the risk to retrieve them in the consumed water and their high activity and grave effects. But prior to usage as drinking water, raw waters are treated and chlorination is a common practice in several countries. As such a treatment can lead to the formation of organochlorine in water, the study of the fate of MTX during chlorination in a batch trial was carried out. The reaction was monitored by dissolved organic carbon (DOC) and by fluorescence and UV spectroscopy. Investigation of by-products formed was done with liquid chromatography/mass spectrometry (LC/MS). Under the given experimental conditions, Methotrexate was eliminated rapidly (t1/2 around 21 min). However, DOC elimination was incomplete. Monitoring with LC-MS showed the formation of a monochlorinated transformation product of MTX. In silico analysis of the proposed transformation products for different carcinogenic, mutagenic and genotoxic endpoints with different software platforms provided no clear evidence that the possible transformation products after chlorination might be more toxic than the parent compound. However, since a number of alerts is altered after chlorination, it cannot be excluded that the toxicity of these transformation products might be modulated compared with the parent compound.

KW - Chemistry

KW - Anti-cancer drug

KW - Chlorination

KW - Drinking water

KW - Transformation product

KW - UV-spectrophotometry

UR - http://www.scopus.com/inward/record.url?scp=84897419865&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/cf9b23e1-4818-3c57-bb36-b79ffa90fd2a/

U2 - 10.1016/j.watres.2014.03.008

DO - 10.1016/j.watres.2014.03.008

M3 - Journal articles

C2 - 24704904

VL - 57

SP - 67

EP - 75

JO - Water Research

JF - Water Research

SN - 0043-1354

ER -