High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

High resolution mass spectrometry (HRMS) was successfully applied to elucidate the structure of a polyfluorinated polyether (PFPE)-based formulation. The mass spectrum generated from direct injection into the MS was examined by identifying the different repeating units manually and with the aid of an instrument data processor. Highly accurate mass spectral data enabled the calculation of higher-order mass defects. The different plots of MW and the nth-order mass defects (up to n = 3) could aid in assessing the structure of the different repeating units and estimating their absolute and relative number per molecule. The three major repeating units were -C2H4O-, -C2F4O-, and -CF2O-. Tandem MS was used to identify the end groups that appeared to be phosphates, as well as the possible distribution of the repeating units. Reversed-phase HPLC separated of the polymer molecules on the basis of number of nonpolar repeating units. The elucidated structure resembles the structure in the published manufacturer technical data. This analytical approach to the characterization of a PFPE-based formulation can serve as a guide in analyzing not just other PFPE-based formulations but also other fluorinated and non-fluorinated polymers. The information from MS is essential in studying the physico-chemical properties of PFPEs and can help in assessing the risks they pose to the environment and to human health

Interspecies comparison of metabolism of two novel prototype PFAS

As a result of proposed global restrictions and regulations on current-use per-and polyfluoroalkyl substances (PFAS), research on possible alternatives is highly required. In this study, phase I in vitro metabolism of two novel prototype PFAS in human and rat was investigated. These prototype chemicals are intended to be safer-by-design and expected to mineralize completely, and thus be less persistent in the environment compared to the PFAS available on the market. Following incubation with rat liver S9 (RL-S9) fractions, two main metabolites per initial substance were produced, namely an alcohol and a short-chain carboxylic acid. While with human liver S9 (HL-S9) fractions, only the short-chain carboxylic acid was detected. Beyond these major metabolites, two and five additional metabolites were identified at very low levels by non-targeted screening for the ether- and thioether-linked prototype chemicals, respectively. Overall, complete mineralization during the in vitro hepatic metabolism of these novel PFAS by HL-S9 and RL-S9 fractions was not observed. The reaction kinetics of the surfactants was determined by using the metabolite formation, rather than the substrate depletion approach. With rat liver enzymes, the formation rates of primary metabolite alcohols were at least two orders of magnitude higher than those of secondary metabolite carboxylic acids. When incubating with human liver enzymes, the formation rates of single metabolite carboxylic acids, were similar or smaller than those experienced in rat. It also indicates that the overall metabolic rate and clearance of surfactants are significantly higher in rat liver than in human liver. The maximum formation rate of the thioether congener exceeded 10-fold that of the ether in humans but were similar in rats. Overall, the results suggest that metabolism of the prototype chemicals followed a similar trend to those reported in studies of fluorotelomer alcohols.</p

Occurrence of emerging persistent and mobile organic contaminants in European water samples

This is the Author’s Accepted Manuscript of the following article: Schulze, S., Zahn, D., Montes, R., Rodil, R., Quintana, J., & Knepper, T. et al. (2019). Occurrence of emerging persistent and mobile organic contaminants in European water samples. Water Research, 153, 80-90. doi: 10.1016/j.watres.2019.01.008The release of persistent and mobile organic chemicals (PMOCs) into the aquatic environment puts the quality of water resources at risk. PMOCs are challenging to analyze in water samples, due to their high polarity. The aim of this study was to develop novel analytical methods for PMOCs and to investigate their occurrence in surface and groundwater samples. The target compounds were culled from a prioritized list of industrial chemicals that were modeled to be persistent, mobile, and emitted into the environment. Analytical screening methods based on mixed-mode liquid chromatography (LC), hydrophilic interaction LC, reversed phase LC, or supercritical fluid chromatography in combination with mass spectrometric detection were successfully developed for 57 target PMOCs and applied to 14 water samples from three European countries. A total of 43 PMOCs were detected in at least one sample, among them 23 PMOCs that have not been reported before to occur in environmental waters. The most prevalent of these novel PMOCs were methyl sulfate, 2-acrylamino-2-methylpropane sulfonate, benzyltrimethylammonium, benzyldimethylamine, trifluoromethanesulfonic acid, 6-methyl-1,3,5-triazine-diamine, and 1,3-di-o-tolylguanidine occurring in ≥50% of the samples at estimated concentrations in the low ng L−1 up to μg L−1 range. The approach of focused prioritization combined with sensitive target chemical analysis proved to be highly efficient in revealing a large suite of novel as well as scarcely investigated PMOCs in surface and groundwaterThis work has been funded by the German BMBF (02WU1347A/B) and the Spanish MINECO/AEI (JPIW2013-117) 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. RM, RR and JBQ also acknowledge Galician Council of Culture, Education and Universities and FEDER/EDRF funding (ED431C2017/36)S

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models

Utilisation of electrospray time-of-flight mass spectrometry for solving complex fragmentation patterns: application to benzoxazinone derivatives

13 pages, 5 figures, 2 tables.-- PMID: 14595855 [PubMed].In this paper we describe the application of electrospray time-of-flight mass spectrometry (ESI-TOFMS) to structural elucidation of the fragment ions formed from a range of natural and synthetic allelochemical derivatives. The extensive mass spectrometric characterisation of ten non-glucosylated benzoxazinone derivatives using this method is described here for the first time. The analytes include six naturally occurring 1,4-benzoxazin-3(4H)-one derivatives, including the hydroxamic acids DIMBOA [2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one] and DIBOA [2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one], lactams HBOA [2-hydroxy-2H-1,4-benzoxazin-3(4H)-one] and HMBOA [2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one], benzoxazolinones BOA [benzoxazolin-2(3H)-one] and MBOA [6-methoxy-benzoxazolin-2(3H)-one] and four synthetic variations, 2H-DIBOA [4-hydroxy-2H-1,4-benzoxazin-3(4H)-one], 2OMe-DIBOA [2-methoxy-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one], 2H-HBOA [2H-1,4-benzoxazin-3(4H)-one] and 2OMe-HBOA [2-methoxy-2H-1,4-benzoxazin-3(4H)-one]. Assignments of the mass spectral fragments were aided by elemental composition calculation results, comparison of structural analogues and background literature, and acquired knowledge regarding feasible structures for the compounds. The influence of substituents on the chemical reactivity of the compounds with respect to the observed MS behaviour over varying nozzle potentials is addressed and, through comparison of the structural analogues, generic fragmentation patterns have also been identified.Financial support provided by the European Commission (5th Framework programme, Project number QLK5-2001-01967), the Foundation of Research, Science and Technology, New Zealand (Post graduate fellowship for Dr. L.S. Bonnington, IQAB0101) and the Ministerio of Ciencia y Tecnologia (funding provided to IIQAB-CSIC, AGL2001-4952-E).Peer reviewe

Determination of two phototransformation products of bentazone using quadrupole time-of-flight mass spectrometry

8 pages, 4 figures, 1 table.-- PMID: 17541562 [PubMed].-- Printed version published Jul 2007.The transformation products 2-isopropylcarbamoyl) phenylsulfamic acid and 2-(1-hydroxypropane-2-yl)-1,2-dihydroindazol-3-one could be determined during the photolysis of the herbicide bentazone. Degradation experiments were carried out with different types of water in a natural sunlight simulating system. Besides the anticipated hydroxylated bentazone, the second transformation product was identified by means of exact mass measurement using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QqToF MS). Both phototransformation products occurred in all water types tested. The required irradiation time was matrix dependent. 2-(Isopropylcarbamoyl)phenylsulfamic acid was detected in a drainage channel in the Ebro river delta (Catalonia, Spain).This research project was funded by the European Union under the Global Change and Ecosystems (FP6) Water Cycle and Soil Related Aspects (AQUATERRA, Project number 505428 GOCE). Financial support from the Spanish Ministry of Education and Science (Project number CTM2005- 25168-E) is also acknowledged.Peer reviewe