Efficient Validation Strategies in Environmental Analytical Chemistry: A Focus on Organic Micropollutants in Water Samples

This article critically reviews analytical method validation and quality control applied to the environmental chemistry field. The review focuses on the determination of organic micropollutants (OMPs), specifically emerging contaminants and pesticides, in the aquatic environment. The analytical technique considered is (gas and liquid) chromatography coupled to mass spectrometry (MS), including high-resolution MS for wide-scope screening purposes. An analysis of current research practices outlined in the literature has been performed, and key issues and analytical challenges are identified and critically discussed. It is worth emphasizing the lack of specific guidelines applied to environmental analytical chemistry and the minimal regulation of OMPs in waters, which greatly affect method development and performance, requirements for method validation, and the subsequent application to samples. Finally, a proposal is made for method validation and data reporting, which can be understood as starting points for further discussion with specialists in environmental analytical chemistry.D.F.-S. acknowledges the Ministerio de Universidades in Spain for his Margarita Salas postdoctoral grant (Ref. MGS/2021/15). The authors from University Jaume I acknowledge financial support from Generalitat Valenciana (Research Group of Excellence Prometeo 2019/040) and Ministerio de Ciencia e Innovación (Ref. PID2021-127451OB-I00). J.B.Q. acknowledges funding provided by Xunta de Galicia (Ref. ED431C 2021/06), the Spanish Agencia Estatal de Investigación – MCIN/AEI/10.13039/501100011033 (Ref. PID2020-117686RB-C32).S

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 persistent and mobile organic contaminants (PMOCs) in water by mixed-mode liquid chromatography-tandem mass spectrometry

The presence of persistent and mobile organic contaminants (PMOC) in aquatic environments has become a matter of concern due to their ability of breaking through natural and anthropogenic barriers, even reaching drinking water. The presence of many of these compounds in surface and drinking water has been reported in screening studies, but there is still a lack of analytical methods capable of quantifying them. Herein, we propose a method combining mixed-mode-solid-phase extraction (MM-SPE) as preconcentration technique and mixed-mode liquid chromatography (MMLC) coupled to tandem mass spectrometry as a determination technique for the quantitative determination of 23 target PMOCs in surface and drinking water samples. When compared to reversed-phase liquid chromatography, the MMLC protocol has proven to be superior in both retentive capabilities and peak shape for ionic compounds, while performing also well for neutrals. The overall method performance was satisfactory with limits of quantification under 50 ng L–1 for most of analytes in both surface and drinking water. The relative standard deviation was lower than 20%, and the average recovery was 78 and 80% in surface and drinking water, respectively. The method was applied to 15 water samples collected in Spain, where 17 out of the 23 target PMOCs were quantified in at least one sample. Among them, 6 chemicals (e.g., benzyltrimethylammonium) are reported and/or quantified here for the first timeThis work has been funded by the Spanish MINECO/AEI (JPIW2013-117, CTM2014-56628-C3-2-R, and CTM2017-84763-C3-2-R) in the frame of the collaborative international consortium (WATERJPI2013 – PROMOTE) of the Water Challenges for a Changing World Joint Programming Initiative (Water JPI) Pilot Call, the Galician Council of Culture, Education and Universities (ED431C2017/36) and FEDER/EDRF fundingS

Wastewater-Based Epidemiology as a New Tool for Estimating Population Exposure to Phthalate Plasticizers

This study proposes the monitoring of phthalate metabolites in wastewater as a nonintrusive and economic alternative to urine analysis for estimating human exposure to phthalates. To this end, a solid-phase extraction–liquid chromatography–tandem mass spectrometry method was developed, allowing for the determination of eight phthalate metabolites in wastewater (limits of quantification between 0.5 and 32 ng L–1). The analysis of samples from the NW region of Spain showed that these substances occur in raw wastewater up to ca. 1.6 μg L–1 and in treated wastewater up to ca. 1 μg L–1. Concentrations in raw wastewater were converted into levels of exposure to six phthalate diesters. For two of them, these levels were always below the daily exposure thresholds recommended by the U.S. Environmental Protection Agency and the European Food Safety Authority. For the other four, however, estimates of exposure surpassed such a threshold (especially the toddler threshold) in some cases, highlighting the significance of the exposure to phthalates in children. Finally, concentrations in wastewater were also used to estimate metabolite concentrations in urine, providing a reasonable concordance between our results and the data obtained in two previous biomonitoring studiesThis work was financed by Spanish Ministry of Economy and Competitiveness (MINECO; project no. CTM2014-56628-C3-2-R), Xunta de Galicia (GRC2013-020 and IGM postdoctoral contract “Plan Galego de Investigación, Innovación e Crecemento 2011–2015”) and FEDER/ERDFS

Modeling Dispersal of UV Filters in Estuaries

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science & Technology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: http://dx.doi.org/10.1021/acs.est.8b03725Lagrangian ocean analysis, where virtual parcels of water are tracked through hydrodynamic fields, provides an increasingly popular framework to predict the dispersal of water parcels carrying particles and chemicals. We conduct the first direct test of Lagrangian predictions for emerging contaminants using (1) the latitude, longitude, depth, sampling date, and concentrations of UV filters in raft cultured mussel (Mytilus galloprovincialis) of the estuary Ria de Arousa, Spain (42.5°N, 8.9°W); (2) a hydrodynamic numerical model at 300 m spatial resolution; and (3) a Lagrangian dispersion scheme to trace polluted water parcels back to pollution sources. The expected dispersal distances (mean ± SD) are 2 ± 1 km and the expected dispersal times (mean ± SD) are 6 ± 2 h. Remarkably, the probability of dispersal of UV filters from potential sources to rafts decreases 5-fold over 5 km. In addition to predicting dispersal pathways and times, this study also provides a framework for quantitative investigations of concentrations of emerging contaminants and source apportionment using turbulent diffusion. In the coastline, the ranges of predicted concentrations of the UV-filters 4-methylbenzylidene-camphor, octocrylene, and benzophenone-4 are 3.2 × 10–4 to 0.023 ng/mL, 2.3 × 10–5 to 0.009 ng/mL, and 5.6 × 10–4 to 0.013 ng/mL, respectively. At the outfalls of urban wastewater treatment plants these respective ranges increase to 8.9 × 10–4 to 0.07 ng/mL, 6.2 × 10–5 to 0.027 ng/mL, and 1.6 × 10–3 to 0.040 ng/mL.This research is supported by the Spanish State Research Agency projects CTM2014-56628-C3-2-R, CTM2014-56628-C3-3-R, CTM2017-84763-C3-2-R, CTM2017-84763-C3-3-R, and CTM2017-90890-REDT (MINECO/AEI/FEDER, EU). This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the National Science Foundation grant number NSF-OCE170005S

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

Transformation products of the high-volume production chemicals 1-vinyl-2-pyrrolidinone and 2-piperazin-1-ylethanamine formed by UV photolysis

This work investigates the reaction of 1-vinyl-2-pyrrolidinone (VP) and 2-piperazin-1-yletanamine (PPE) under UV radiation. Both substances are high-volume production chemicals (production >1000 tons/year) widely used in polymers, coatings and a wide array of applications, which have been classified as mobile chemicals and which can then lead to the formation of persistent and mobile transformation products (TPs). Thus, their reaction with UV light was studied by means of liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-QTOF-MS). Both compounds presented a high reactivity, the VP quantum yield was 0.28 mol/E; whereas, PPE had a quantum yield notably higher than 1 (16 mol/E). Five and 7 TPs were identified for VP and PPE, respectively. Some of them had been already reported in literature due to sunlight photodegradation or other oxidation processes, but most of them are reported here for the first time. Finally, the acute and chronical toxicity of precursors and TPs were estimated using two quantitative structure-activity relationship (QSAR) software tools which led to some discrepancies in the estimations, pointing to the need for experimental toxicity assays for these compoundsThis work was supported by the Water Challenges for a Changing World Joint Program Initiative (Water JPI) Pilot Call (ref. WATERJPI2013 – PROMOTE), funded by the Spanish Ministry of Economy and Competitiveness/Spanish Agencia Estatal de Investigación (refs. JPIW 2013-117, CTM2017-84763-C3-2-R and PID2020-117686RB-C32). We also acknowledge the Galician Council of Culture, Education and Universities (ref. ED431C2021/06). 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

Chronic exposure to environmentally relevant levels of simvastatin disrupts zebrafish brain gene signaling involved in energy metabolism

Simvastatin (SIM), a hypocholesterolaemic drug belonging to the statins group, is a widely prescribed pharmaceutical for prevention of cardiovascular diseases. Several studies showed that lipophilic statins, as SIM, cross the blood-brain barrier and interfere with the energy metabolism of the central nervous system in humans and mammalian models. In fish and other aquatic organisms, the effects of SIM on the brain energy metabolism are unknown, particularly following exposure to low environmentally relevant concentrations. Therefore, the present study aimed at investigating the influence of SIM on gene signaling pathways involved in brain energy metabolism of adult zebrafish (Danio rerio) following chronic exposure (90 days) to environmentally relevant SIM concentrations ranging from 8 ng/L to 1000 ng/L. Real-time PCR was used to determine the transcript levels of several genes involved in different pathways of the brain energy metabolism (glut1b, gapdh, acadm, accα, fasn, idh3a, cox4i1, and cox5aa). The findings here reported integrated well with ecological and biochemical responses obtained in a parallel study. Data demonstrated that SIM modulates transcription of key genes involved in the mitochondrial electron transport chain, in glucose transport and metabolism, in fatty acid synthesis and β-oxidation. Further, SIM exposure led to a sex-dependent transcription profile for some of the studied genes. Overall, the present study demonstrated, for the first time, that SIM modulates gene regulation of key pathways involved in the energy metabolism in fish brain at environmentally relevant concentrationsThis study was developed under the project Nor-Water -Poluentes emergentes nas águas da Galiza-Norte de Portugal: novas ferramentas para gestão de risco [Reference: 0725_NOR_WATER_1_P], financed by Programa de Cooperação Interreg Portugal/Espanha, (POCTEP) 2014–2020. The study was also supported by the National Funds through Portuguese Foundation for Science and Technology (FCT) under the projects [UID/Multi/04423/2019 and UID/AGR/04033/2013]. S. Barros was supported by the doctoral fellowship [PD/BD/143090/2018] from FCT. J.B. Quintana acknowledges the financial support of Spanish “Agencia Estatal de Investigación” [ref. CTM2017-84763-C3-R-2] and Xunta de Galicia [ref. ED431C2017/36], both co-funded by FEDER/ERDFS

Bioaccumulation of UV filters in Mytilus galloprovincialis mussel

This is the postprint (accepted manuscript) version of the article published in Chemosphere https://doi.org/10.1016/j.chemosphere.2017.09.144In this study the bioaccumulation kinetics of organic UV filters, such as 4-MBC, BP-3, BP-4, OC and OD-PABA in wild Mytilus galloprovincialis mussels was investigated. The uptake and accumulation of waterborne 4-MBC, BP-4 and OC was very rapid, and after only 24 h of exposure to 1 μg L−1, the tissular concentrations were 418, 263 and 327 μg kg−1d.w., respectively. The kinetics of bioaccumulation of BP-4 and OC significantly fitted to an asymptotic model with BCF values of 905 L kg−1 and 2210 L kg−1, respectively. Measured bioaccumulation of the hydrophilic chemical BP-4 was much higher than predicted by Kow-based bioconcentration models, which would lead to a marked underestimation of actual risk. On the other hand, the patterns of uptake found for BP-3 and OD-PABA suggest biotransformation ability of mussels for these two chemicalshis work was financed by the Galician Government (Xunta de Galicia) through the Research Project 10MDS700006PR and GRC2013-020, by the Spanish Government through the Research Projects CTM2016-77945-C3 and CTM2014-56628-C3-2-R, and FEDER/ERDF. The first two authors were granted with an FPU and an FPI fellowships, respectively, from the Spanish GovernmentS

Determination of 18 organophosphorus flame retardants/plasticizers in mussel samples by matrix solid-phase dispersion combined to liquid chromatography-tandem mass spectrometry

This study presents the development and validation of a new analytical method based on matrix solid-phase dispersion (MSPD), integrating sample extraction and clean-up in one single step, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 18 organophosphorus flame retardants and/or plasticizers (OPEs) in marine mussel (Mytilus edulis and Mytilus galloprovincialis) samples. Among these OPEs, 5 (tetraethyl 1,2-ethanediylbis(phosphonate), 6H-dibenzo[c,e] [1,2]oxaphosphinine 6-oxide, tris(2,3-dibromopropyl) phosphate, 2,2-propanediyldi-4,1-phenylene bis(phosphate) and resorcinol bis(diphenyl phosphate)) are considered here for the first time in marine samples. Different parameters affecting the MSPD (clean-up sorbent and elution solvent) were optimized to obtain a good compromise between analyte recoveries and extract clean-up. Also, particular attention was paid to tackle blank issues. The overall method was validated in terms of trueness, precision and detection and quantification limits. Percentages of recovery varied from 69% to 122% with relative standard deviations below 24%. Detection limits ranged from 0.06 to 5 ng g−1 and quantification limits from 0.19 to 17 ng g−1 dry weight. Finally, the method was applied to the analysis of 7 mussel samples collected in the coast of Galicia (Spain). 8 OPEs were detected in these samples at concentrations ranging from the LOQ to 291 ng g−1 dry weight.This work was financially supported by the Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ref. ED431C2017/36 and Verónica Castro predoctoral contract, ref. ED481A-2017/156), cofunded by FEDER/ERDFS