Monitoring of methotrexate chlorination in water.
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.
Nîmes University, Rue du docteur George Salan, 30000 Nîmes, France; INSERM U1085-IRSET, LERES, France; EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, CS 74312, 35043 Rennes Cedex, France. Electronic address: benoit.roig@unimes.fr.
B
B
Roig
EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, CS 74312, 35043 Rennes Cedex, France.
B
B
Marquenet
EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, CS 74312, 35043 Rennes Cedex, France.
I
I
Delpla
EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, CS 74312, 35043 Rennes Cedex, France; University of Waterloo, Department of Chemistry, 200 University Ave., Waterloo, ON N2L 3G1, Canada.
V
V
Bessonneau
INSERM U1085-IRSET, LERES, France; EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, CS 74312, 35043 Rennes Cedex, France.
A
A
Sellier
Institute for Sustainable and Environmental Chemistry, Leuphana Universität, Lüneburg, Germany.
C
C
Leder
INSERM U1085-IRSET, LERES, France; EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, CS 74312, 35043 Rennes Cedex, France.
O
O
Thomas
Institute for Sustainable and Environmental Chemistry, Leuphana Universität, Lüneburg, Germany.
R
R
Bolek
Institute for Sustainable and Environmental Chemistry, Leuphana Universität, Lüneburg, Germany.
K
K
Kummerer
D002853:Chromatography, Liquid; D004784:Environmental Monitoring; D054879:Halogenation; D013058:Mass Spectrometry; D008727:Methotrexate / Q000032:analysis* / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000737:chemistry; D018508:Water Purification
D014874:Water Pollutants, Chemical; D008727:Methotrexate
Anti-cancer drug; Chlorination; Drinking water; Transformation product; UV-spectrophotometry