Free chlorine reactions of angiotensin II receptor antagonists: Kinetics study, transformation products elucidation and in-silico ecotoxicity assessment

This is the Author’s Accepted Manuscript of the following article: Carpinteiro, I., Castro, G., Rodríguez, I., & Cela, R. (2018). Free chlorine reactions of angiotensin II receptor antagonists: Kinetics study, transformation products elucidation and in-silico ecotoxicity assessment. Science Of The Total Environment, 647, 1000-1010. doi: 10.1016/j.scitotenv.2018.08.082Angiotensin II receptor antagonists (ARA II) are widely employed in the treatment of hypertension-related diseases. Because of their partial metabolization and limited biodegradability, these drugs have become ubiquitous pollutants in the aquatic environment, including surface water. This research evaluated the reactivity of the ARA II drugs: irbesartan (IRB), losartan (LOS) telmisartan (TEL) and valsartan (VAL) with free chlorine. Responses of parent compounds and their transformation products (TPs) were followed by liquid chromatography (LC) with quadrupole (Q) time-of-flight (TOF) mass spectrometry. Degradation experiments were carried out using ultrapure and river water samples, adjusted at different pHs and, in some cases, adding a small amount (ng mL−1 level) of bromide salts. Whilst TEL and VAL remained stable in presence of relatively high concentrations of free chlorine (10 mg L−1), IRB and LOS were removed according to a pseudo-first order kinetics model. Considering an initial chlorine concentration of 10 mg L−1, their half-lives varied between 6 and 734 min, depending mostly on the water pH. IRB reacted with free chlorine through hydroxylation processes, with and without molecular cleavage and re-arrangements in the imidazolone ring. Its TPs showed a lower in-silico predicted toxicity than the parent drug. In case of LOS, two major competitive degradation routes were identified. They involved replacement of the methanol group attached to the imidazole cycle by chlorine or bromine, and the cleavage of this cycle with removal of the chlorinated carbon and the nitrogen in alpha position. The TPs generated following the first route are predicted to be more toxic than LOSThis study was supported by Xunta de Galicia (grant GRC-ED431C 2017/36), and the Spanish Government (grant CTQ2015-68660-P). I.C. acknowledges a postdoctoral fellowship to Xunta de GaliciaS

Reaction of diazepam and related benzodiazepines with chlorine. Kinetics, transformation products and in-silico toxicological assessment

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 and in-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 licenseIn 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 factThis 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 governmentS

Determination of N-Nitrosamines by Gas Chromatography Coupled to Quadrupole–Time-of-Flight Mass Spectrometry in Water Samples

An analytical method based on high-resolution quadrupole–time-of-flight (QToF) mass spectrometry has been developed as an alternative to the classical method, using a low-resolution ion trap (IT) analyzer to reduce interferences in N-nitrosamines determination. Extraction of the targeted compounds was performed by solid-phase extraction (SPE) following the United States Environmental Protection Agency (USEPA) -521 method. First, both electron impact (EI) and positive chemical ionization (PCI) using methane as ionization gas were compared, along with IT and QToF detection. Then, parameters such as limits of detection (LOD) and quantification (LOQ), linearity, and repeatability were assessed. The results showed that the QToF mass analyzer combined with PCI was the best system for the determination of the N-nitrosamines, with instrumental LOD and LOQ in the ranges of 0.2–4 and 0.6–11 ng mL−1, respectively, which translated into method LOD and LOQ in the ranges of 0.2–1.3 and 0.6–3.9 ng L−1, respectively. The analysis of real samples showed the presence of 6 of the N-nitrosamines in influent, effluent, and tap water. N-nitrosodimethylamine (NDMA) was quantified in all the analyzed samples at concentrations between 1 and 27 ng L−1. Moreover, four additional nitrosamines were found in tap and wastewater samplesThis research was funded by Xunta de Galicia (references EM2014/004 and ED431C2017/36), Spanish Agencia Estatal de Investigación (reference CTM2017-84763-C3-R-2), and European Regional Development Fund (FEDER/ERDF) funds. I.C. acknowledges her postdoctoral formation grant from Xunta de Galicia governmentS

Nuevos desarrollos analíticos para la determinación de compuestos orgánicos en matrices medioambientales y alimentarias

En esta Tesis doctoral se describe el desarrollo y mejora de metodología analítica para la determinación de tres familias de compuestos (derivados de 2-hidroxibenzotriazol, fungicidas y etilfenoles) en diferentes matrices ambientales (agua, suelo, sedimento y polvo) y en muestras de vino. Se ha incidido en aspectos tales como la mejora de la selectividad, la reducción en los costes y la generación de residuos, así como en la simplificación de la manipulación de las muestras y la reducción del tiempo de preparación de las muestras. Para matrices líquidas, las metodologías utilizadas fueron la extracción en fase sólida y las basadas en técnicas de microextracción. Para matrices sólidas, se emplearon la extracción con disolventes presurizados y dispersión da matriz en fase sólida. Estas técnicas se combinaron con procedimientos de determinación mediante cromatografía de gases e líquida seguidas de espectrometría de masas, simple ou en tándem

Residues of anilinopyrimidine fungicides and suspected metabolites in wine samples

The coexistence of the anilinopyrimidine fungicides pyrimethanil (PYR) and cyprodinil (CYP), and suspected metabolites in wine samples was investigated by liquid chromatography (LC) with tandem mass spectrometry (MS/MS), based on triple quadrupole (QqQ) and quadrupole time-of-flight (QTOF) MS instruments. For the first time, quantitative data obtained after solid-phase extraction (SPE) of wine samples have demonstrated the systematic presence of 4-hydroxyanilino derivatives of PYR and CYP in wines containing residues of parent fungicides, at concentrations from 0.2 to 58 ng mL−1. Higher concentration ratios (hydroxylated derivative/active fungicide) were measured in red than in white wines, particularly in case of PYR. On average, the concentrations of PYR-4OH were twice those measured for PYR in red wines. A targeted search of hydroxyl derivatives in wine extracts by LC-QTOF-MS showed the existence of additional hydroxylation positions in the pyrimidine ring and/or in the alkyl substituents bond to this cycle in the structure of both anti-botrytis fungicides. Moreover, free and glycosylated forms of the hydroxylated metabolites for both fungicides coexist in wine samples. In case of CYP, it is proved that hydroxylated and glycosylated metabolites are already present in grapes before vinificationL.P.M acknowledges a FPU grant to the Spanish Ministry of Science. The study was supported by Xunta de Galicia, Spanish Government and EU funds through grants GRC-ED431C 2017/36, PGC2018-094613-B-I00 and the Interreg SUDOE VINOVERT projectS

Combination of different chromatographic and sampling modes for high-resolution mass spectrometric screening of organic microcontaminants in water

This study explores the combination of two sampling strategies (polar organic compounds integrative sampler (POCIS) vs. spot sampling) and four chromatographic retention modes (reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), mixed-mode liquid chromatography (MMLC) and supercritical fluid chromatography (SFC)) for high-resolution mass spectrometry (HRMS) screening of organic pollutants in water samples. To this end, a suspect screening approach, using iterative data-dependent tandem mass spectrometry (MS/MS) driven by a library of 3227 chemicals (including pharmaceuticals, pesticides, drugs of abuse, human metabolites, industrial chemicals and other pollutants), was employed. Results show that POCIS can afford a larger number of positive identifications as compared to spot sampling. On the other hand, the best suited retention mechanisms, in terms of identified analytes, are SFC, and followed by RPLC, MMLC and HILIC. However, the best combination (POCIS + SFC) would only allow the identification of 67% of the detected analytes. Thus, the combination of the two sampling strategies, spot and passive sampling, with two orthogonal retention mechanisms, RPLC and SFC, is proposed in order to maximize the number of analytes detected (89%). This strategy was applied to different surface water (river and estuary) samples from Galicia (NW Spain). A total of 155 compounds were detected at a confidence level 2a, from which the major class was pharmaceuticals (61%).This research was funded by Xunta de Galicia (ED431C2017/36 and V.C. predoctoral contract: ED481A-2017/156), the Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-R-2 and CTM2017-90980-REDT) and FEDER/ERDF funds. This research has been co-financed by the European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014-2020 (ref. 0725_NOR_WATER_1_P). It only reflects the author’s view; thus, Programme authorities are not liable for any use that may be made of the information contained therein.S