27 research outputs found
Identifying Complex Mixtures in the Environment with Cheminformatics and Non-targeted High Resolution Mass Spectrometry
Presentation at the Society of Environmental Toxicology and Chemistry (SETAC) North America Meeting Sep 201
How Biotransformation Influences Toxicokinetics of Azole Fungicides in the Aquatic Invertebrate <i>Gammarus pulex</i>
Biotransformation
is a key process that can greatly influence the
bioaccumulation potential and toxicity of organic compounds. In this
study, biotransformation of seven frequently used azole fungicides
(triazoles: cyproconazole, epoxiconazole, fluconazole, propiconazole,
tebuconazole and imidazoles: ketoconazole, prochloraz) was investigated
in the aquatic invertebrate <i>Gammarus pulex</i> in a 24
h exposure experiment. Additionally, temporal trends of the whole
body internal concentrations of epoxiconazole, prochloraz, and their
respective biotransformation products (BTPs) were studied to gain
insight into toxicokinetic processes such as uptake, elimination and
biotransformation. By the use of high resolution tandem mass spectrometry
in total 37 BTPs were identified. Between one (ketoconazole) and six
(epoxiconazole) BTPs were identified per parent compound except for
prochloraz, which showed extensive biotransformation reactions with
18 BTPs detected that were mainly formed through ring cleavage or
ring loss. In general, most BTPs were formed by oxidation and conjugation
reactions. Ring loss or ring cleavage was only observed for the imidazoles
as expected from the general mechanism of oxidative ring openings
of imidazoles, likely affecting the bioactivity of these BTPs. Overall,
internal concentrations of BTPs were up to 3 orders of magnitude lower
than that of the corresponding parent compound. Thus, biotransformation
did not dominate toxicokinetics and only played a minor role in elimination
of the respective parent compound, with the exception of prochloraz
Screening of Lake Sediments for Emerging Contaminants by Liquid Chromatography Atmospheric Pressure Photoionization and Electrospray Ionization Coupled to High Resolution Mass Spectrometry
We developed a multiresidue method for the target and suspect screening
of more than 180 pharmaceuticals, personal care products, pesticides,
biocides, additives, corrosion inhibitors, musk fragrances, UV light
stabilizers, and industrial chemicals in sediments. Sediment samples
were freeze-dried, extracted by pressurized liquid extraction, and
cleaned up by liquid–liquid partitioning. The quantification
and identification of target compounds with a broad range of physicochemical
properties (log <i>K</i><sub>ow</sub> 0–12) was carried
out by liquid chromatography followed by electrospray ionization (ESI)
and atmospheric pressure photoionization (APPI) coupled to high resolution
Orbitrap mass spectrometry (HRMS/MS). The overall method average recoveries
and precision are 103% and 9% (RSD), respectively. The method detection
limits range from 0.010 to 4 ng/g<sub>dw</sub>, while limits of quantification
range from 0.030 to 14 ng/g<sub>dw</sub>. The use of APPI as an alternative
ionization source helped to distinguish two isomeric musk fragrances
by means of different ionization behavior. The method was demonstrated
on sediment cores from Lake Greifensee located in northeastern Switzerland.
The results show that biocides, musk fragrances, and other personal
care products were the most frequently detected compounds with concentrations
ranging from pg/g<sub>dw</sub> to ng/g<sub>dw</sub>, whereas none
of the targeted pharmaceuticals were found. The concentrations of
many urban contaminants originating from wastewater correlate with
the highest phosphorus input into the lake as a proxy for treatment
efficiency. HRMS enabled a retrospective analysis of the full-scan
data acquisition allowing the detection of suspected compounds like
quaternary ammonium surfactants, the biocide triclocarban, and the
tentative identification of further compounds without reference standards,
among others transformation products of triclosan and triclocarban
Alleviating the Reference Standard Dilemma Using a Systematic Exact Mass Suspect Screening Approach with Liquid Chromatography-High Resolution Mass Spectrometry
In
this study, the efficiency of a suspect screening strategy using
liquid chromatography-high resolution mass spectrometry (LC-HRMS)
without the prior purchase of reference standards was systematically
optimized and evaluated for assessing the exposure of rarely investigated
pesticides and their transformation products (TPs) in 76 surface water
samples. Water-soluble and readily ionizable (electrospray ionization)
substances, 185 in total, were selected from a list of all insecticides
and fungicides registered in Switzerland and their major TPs. Initially,
a solid phase extraction-LC-HRMS method was established using 45 known,
persistent, and high sales volume pesticides. Seventy percent of these
target substances had limit of quantitation (LOQ) < 5 ng L<sup>–1</sup>. This compound set was then used to develop and optimize
a HRMS suspect screening method using only the exact mass as a priori
information. Thresholds for blank subtraction, peak area, peak shape,
signal-to-noise, and isotopic pattern were applied to automatically
filter the initially picked peaks. The success rate was 70%; false
negatives mainly resulted from low intense peaks. The optimized approach
was applied to the remaining 140 substances. Nineteen additional substances
were detected in environmental samples, two TPs for the first time
in the environment. Sixteen substances were confirmed with reference
standards purchased subsequently, while three TP standards could be
obtained from industry or other laboratories. Overall, this screening
approach was fast and very successful and can easily be expanded to
other micropollutant classes for which reference standards are not
readily accessible such as TPs of household chemicals
Covalent Binding of Sulfamethazine to Natural and Synthetic Humic Acids: Assessing Laccase Catalysis and Covalent Bond Stability
Sulfonamide antibiotics form stable
covalent bonds with quinone
moieties in organic matter via nucleophilic addition reactions. In
this work, we combined analytical electrochemistry with trace analytics
to assess the catalytic role of the oxidoreductase laccase in the
binding of sulfamethazine (SMZ) to Leonardite humic acid (LHA) and
to four synthetic humic acids (SHAs) polymerized from low molecular
weight precursors and to determine the stability of the formed bonds.
In the absence of laccase, a significant portion of the added SMZ
formed covalent bonds with LHA, but only a very small fraction (<0.4%)
of the total quinone moieties in LHA reacted. Increasing absolute,
but decreasing relative concentrations of SMZ–LHA covalent
bonds with increasing initial SMZ concentration suggested that the
quinone moieties in LHA covered a wide distribution in reactivity
for the nucleophilic addition of SMZ. Laccase catalyzed the formation
of covalent bonds by oxidizing unreactive hydroquinone moieties in
LHA to reactive, electrophilic quinone moieties, of which a large
fraction (5%) reacted with SMZ. Compared to LHA, the SHA showed enhanced
covalent bond formation in the absence of laccase, suggesting a higher
reactivity of their quinone moieties toward nucleophilic addition.
This work supports that binding to soil organic matter (SOM) is an
important process governing the fate, bioactivity, and extractability
of sulfonamides in soils
Reactions of a Sulfonamide Antimicrobial with Model Humic Constituents: Assessing Pathways and Stability of Covalent Bonding
The mechanism of covalent bond formation of the model
sulfonamide
sulfathiazole (STZ) and the stronger nucleophile <i>para</i>-ethoxyaniline was studied in reactions with model humic acid constituents
(quinones and other carbonyl compounds) in the absence and presence
of laccase. As revealed by high resolution mass spectrometry, the
initial bonding of STZ occurred by 1,2- and 1,4-nucleophilic additions
of the aromatic amino group to quinones resulting in imine and anilinoquinone
formation, respectively. Experiments using the radical scavenger <i>tert</i>-butyl-alcohol provided the same products and similar
formation rates as those without scavenger indicating that probably
not radical coupling reactions were responsible for the initial covalent
bond formation. No addition with nonquinone carbonyl compounds occurred
within 76 days except for a slow 1,4-addition to the β-unsaturated
carbonyl 1-penten-3-one. The stability of covalent bonds against desorption
and pressurized liquid extraction (PLE) was assessed. The recovery
rates showed no systematic differences in STZ extractability between
the two product types. This suggests that the strength of bonding
is not controlled by the initial type of bond, but by the extent of
subsequent incorporation of the reaction product into the formed polymer.
This incorporation was monitored for <sup>15</sup>N aniline by <sup>1</sup>H–<sup>15</sup>N HMBC NMR spectroscopy. The initial
1,2- and 1,4-addition bonds were replaced by stronger heterocyclic
forms with increasing incubation time. These processes could also
hold true for soils, and a slow nonextractable residue formation with
time could be related to a slow increase of the amount of covalently
bound sulfonamide and the strength of bonding
Adding Complex Expert Knowledge into Chemical Databases: Transforming Surfactants in Wastewater
Presentation at American Chemical Society meeting March 201
Life history and microsatellite data
Contains four workbooks, with two types of data for two lakes. Those workbooks called "life_table" contain the results of our Pb exposure life history experiment. Each row represents one individual, which was kept in its own jar. Columns identify each clone, clone age, and Pb treatment. The columns labeled with day numbers give the number of live births counted on that day. Deaths are recorded as NAs: the first NA appears on the day that an animal was found dead. The workbooks called "msats" contain the microsatellite data retrieved from sedimentary eggs. Each row represents one egg. A column gives the year the egg was produced, and for Greifensee, another column gives the species identity. The remainder of the columns give the diploid microsatellite genotype of each egg. The names of the columns correspond to the names of the markers
Mechanistic Understanding of the Synergistic Potential of Azole Fungicides in the Aquatic Invertebrate <i>Gammarus pulex</i>
Azole
fungicides are known inhibitors of the important enzyme class
cytochrome P450 monooxygenases (CYPs), thereby influencing the detoxification
of co-occurring substances via biotransformation. This synergism in
mixtures containing an azole has mostly been studied by effect measurements,
while the underlying mechanism has been less well investigated. In
this study, six azole fungicides (cyproconazole, epoxiconazole, ketoconazole,
prochloraz, propiconazole, and tebuconazole) were selected to investigate
their synergistic potential and their CYP inhibition strength in the
aquatic invertebrate <i>Gammarus pulex</i>. The strobilurin
fungicide azoxystrobin was chosen as co-occurring substrate, and the
synergistic potential was measured in terms of internal concentrations
of azoxystrobin and associated biotransformation products (BTPs).
Azoxystrobin is biotransformed by various reactions, and 18 BTPs were
identified. By measuring internal concentrations of azoxystrobin and
its BTPs with high-resolution tandem mass spectrometry in the presence
and absence of azole fungicides followed by toxicokinetic modeling,
we showed that the inhibition of CYP-catalyzed biotransformation reactions
indeed played a role for the observed synergism. However, synergism
was only observed for prochloraz at environmentally realistic concentrations.
Increased uptake rate constants, an increase in the total internal
concentration of azoxystrobin and its BTPs, in vivo assays for measuring
CYP activities, and <i>G. pulex</i> video-tracking suggested
that the 2-fold increase in bioaccumulation, and, thereby, the raised
toxicity of azoxystrobin in the presence of prochloraz is not only
caused by inhibited biotransformation but even more by increased azoxystrobin
uptake induced by hyperactivity
MOESM4 of MetFrag relaunched: incorporating strategies beyond in silico fragmentation
Additional file 4. Top 1 ranks of MetFrag2.2. combined with CFM--ID This figure shows the distribution of the number of top 1 ranks with different weights (100 drawn randomly between 0 and 1) for MetFrag2.2 and CFM--ID. Lightestyellow dot marks the maximum, 62 top 1 ranks at MetFrag = 0.67 and CFM-ID = 0.33. The red dot at the right marks the minimum, 36 top 1 ranks at MetFrag = 0.997 and CFM-ID = 0.003. The most left dot marks 49 top 1 ranks at MetFrag = 0.02 and CFM-ID = 0.98