RT Journal Article
T1 Reaction of diazepam and related benzodiazepines with chlorine. Kinetics, transformation products and in-silico toxicological assessment
A1 Carpinteiro Botana, María Inmaculada
A1 Rodil Rodríguez, María del Rosario
A1 Quintana Álvarez, José Benito
A1 Cela Torrijos, Rafael
K1 Psychoactive drugs
K1 High resolution mass spectrometry
K1 Water treatment
K1 Disinfection by-products
AB In this work, the reaction of four benzodiazepines (diazepam, oxazepam, nordazepam and temazepam) during water chlorination was studied by means of liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-QTOF-MS). For those compounds that showed a significant degradation, i.e. diazepam, oxazepam and nordazepam, parameters affecting to the reaction kinetics (pH, chlorine and bromide level) were studied in detail and transformation products were tentatively identified. The oxidation reactions followed pseudofirst-order kinetics with rate constants in the range of 1.8–42.5 M−1 s−1, 0.13–1.16 M−1 s−1 and 0.04–20.4 M−1 s−1 corresponding to half-life values in the range of 1.9–146 min, 1.8–87 h and 2.5–637 h for oxazepam, nordazepam and diazepam, respectively, depending of the levels of studied parameters. Chlorine and pH affected significantly the reaction kinetics, where an increase of the pH resulted into a decrease of the reaction rate, whereas higher chlorine dosages led to faster kinetics, as expected in this case. The transformation of the studied benzodiazepines occurs mainly at the 1,4-diazepine 7-membered-ring, resulting in ring opening to form benzophenone derivatives or the formation of a 6-membered pyrimidine ring, leading to quinazoline derivatives. The formation of these by-products was also tested in real surface water samples observing kinetics of oxazepam degradation slower in river than in creek water, while the degradation of the two other benzodiazepines occurred only in the simpler sample (creek water). Finally, the acute and chronical toxicity and mutagenicity of precursors and transformation products were estimated using quantitative structure-activity relationship (QSAR) software tools: Ecological Structure Activity Relationships (ECOSAR) and Toxicity Estimation Software Tool (TEST), finding that some transformation products could be more toxic/mutagenic than the precursor drug, but additional test would be needed to confirm this fact
PB Elsevier
SN 0043-1354
YR 2017
FD 2017-05-03
LK http://hdl.handle.net/10347/17431
UL http://hdl.handle.net/10347/17431
LA eng
NO Carpinteiro, I., Rodil, R., Quintana, J., & Cela, R. (2017). Reaction of diazepam and related benzodiazepines with chlorine. Kinetics, transformation products and in-silico toxicological assessment. Water Research, 120, 280-289. doi: 10.1016/j.watres.2017.04.063
NO This is the Author’s Accepted Manuscript of the following article: I. Carpinteiro, R. Rodil, J.B. Quintana, R.Cela. Reaction of diazepam and related benzodiazepines with chlorine. Kinetics, transformation products andin-silico toxicological assessment Water Research 120 (2017) 280-289 with DOI: 10.1016/j.watres.2017.04.063© Elsevier 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
NO This study has been supported by Xunta de Galicia (EM2014-004 and GRC2013-020) and FEDER/ERDF. I.C. acknowledges her postdoctoral formation grant to Xunta de Galicia government
DS Minerva
RD 23 abr 2026