Suspect and untargeted screening of bisphenol S metabolites produced by in vitro human liver metabolism

Gys, Celine; Kovačić, Ana; Huber, Carolin; Lai, Foon Yin; Heath, Ester

doi:10.1016/j.toxlet.2018.05.034

Cited by 19 publications

(9 citation statements)

References 36 publications

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Section: Resultssupporting

confidence: 65%

“…BPS sulfate (BPS+SO 3 ) and hydroxylated BPS sulfate (BPS +O+SO 3 ) were detected at 5.9 min (m/z 328.9797) and 5.4 min (m/z 344.9744), respectively. These glucuronide and sulfate conjugates, with the exception of BPS+O+SO 3 , have been previously reported in human liver and intestinal microsomes and recombinant CYP enzymes; 30,31 however, no GSH adducts were reported.…”

Section: ■ Results and Discussionsupporting

confidence: 60%

“…BPS formed one hydroxylated metabolite (BPS+O) at 7.5 min (m/z 265.0182) and one dihydroxylated metabolite (BPS +2O) at 6.3 min (m/z 281.0127) (Figure S6), both of which have been previously reported in vitro. 30 BPS also formed two dimers (BPS-2H) at 11.4 and 13.2 min (Figure S1). The later eluting dimer (Figure S7) had product ions at m/z 265.0197 and 264.0100, corresponding to C 12 H 9 O 5 S − and C 12 H 8 O 5 S •− , respectively, proving it to be the C−O dimer.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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In Vitro Metabolism of Five Bisphenol A Analogs Studied by LC-HRMS/MS

Ousji

Sleno

2020

J. Am. Soc. Mass Spectrom.

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Bisphenol A (BPA) structural analogs are increasingly used as alternatives in many industrial applications, due to growing evidence of BPA-related toxicity. Despite their widespread use, little is known about the biotransformation of these BPA analogs in the body. In this study, the in vitro metabolism of five BPA analogs (bisphenol AF, bisphenol F, bisphenol S, cumylphenol, and tetramethylbisphenol F) were investigated, using human and rat liver fractions, to evaluate the formation of phase I and phase II metabolites. Liquid chromatography high-resolution tandem mass spectrometry was employed to separate and characterize over 50 metabolites, many of which were not previously reported. The structures of all detected oxidative metabolites, dimers, GSH adducts, glucuronide, and sulfate conjugates were elucidated. A biphenyl solid-core chromatographic column was utilized for the separation of all metabolites, with a subsequent method, on a F5 column, specifically optimized for the separation of dimers formed via oxidative metabolism. There are several examples in this work where the combination of high chromatographic resolution and tandem mass spectrometry were necessary to distinguish between isomeric metabolites and conjugates.

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Section: Resultssupporting

confidence: 65%

Section: ■ Results and Discussionsupporting

confidence: 60%

Section: ■ Results and Discussionmentioning

confidence: 99%

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In Vitro Metabolism of Five Bisphenol A Analogs Studied by LC-HRMS/MS

Ousji

Sleno

2020

J. Am. Soc. Mass Spectrom.

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“…Finally, we applied McSearch in a real application to annotate the MS 2 spectra of unknown xenobiotic metabolite derivatives of methylenedioxypyrovalerone (MDPV), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA). − Among the 19 experimental MS 2 spectra, 18 metabolites can be directly annotated using the McSearch platform and agree with the literature, including both one- and two-step biotransformation reactions. Figure , Figure S4, and Figure S5, respectively, show the metabolism pathways of these metabolites and the McSearch score-based spectral networks of these metabolites in the MDPV, BPS, and TBBPA classes.…”

Section: Resultsmentioning

confidence: 99%

Retrieving and Utilizing Hypothetical Neutral Losses from Tandem Mass Spectra for Spectral Similarity Analysis and Unknown Metabolite Annotation

Xing

Yin³

et al. 2020

Anal. Chem.

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Spectral similarity comparison through tandem mass spectrometry (MS2) is a powerful approach to annotate known and unknown metabolic features in mass spectrometry (MS)-based untargeted metabolomics. In this work, we proposed the concept of hypothetical neutral loss (HNL), which is the mass difference between a pair of fragment ions in a MS2 spectrum. We demonstrated that HNL values contain core structural information that can be used to accurately assess the structural similarity between two MS2 spectra. We then developed the Core Structure-based Search (CSS) algorithm based on HNL values. CSS was validated with sets of hundreds of randomly selected metabolites and their reference MS2 spectra, showing significantly improved correlation between spectral and structural similarities. Compared to state-of-the-art spectral similarity algorithms, CSS generates better ranking of structurally relevant chemicals among false positives. Combining CSS, HNL library, and biotransformation database, we further developed Metabolite core structure-based Search (McSearch), a novel computational solution to facilitate the annotation of unknown metabolites using the reference MS2 spectra of their structural analogs. McSearch generates better results in the Critical Assessment of Small Molecule Identification (CASMI) 2017 data set than conventional unknown feature annotation programs. McSearch was also tested in experimental MS2 data of xenobiotic metabolite derivatives belonging to three different metabolic pathways. Our results confirmed that McSearch can better capture the underlying structural similarity between MS2 spectra. Overall, this work provides a novel direction for metabolite annotation via HNL values, paving the way for annotating metabolites using their structurally similar compounds.

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“…To close this gap and improve the annotation of pesticide and other contaminant metabolites, we propose to use in vitro metabolization experiments as a cost- and time-effective approach to generate and analyze these compounds, from which the relevant MS 2 and retention time information can be obtained. In vitro metabolism experiments using liver homogenates were applied in drug discovery and detection of psychoactive substances but have also been applied in the context of HBM studies of contaminants. − Yet, all of these studies have only focused on a small number of similar compounds, and the applied methods have used time-consuming manual steps, calling for automation of the data processing for efficient application with screening methods. Even without an extensive metabolic pathway study or a complete structure elucidation, such data can be used to annotate metabolites in human cohort studies.…”

Section: Introductionmentioning

confidence: 99%

Improving the Screening Analysis of Pesticide Metabolites in Human Biomonitoring by Combining High-Throughput In Vitro Incubation and Automated LC–HRMS Data Processing

et al. 2021

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There is a current need to monitor human exposure to a large number of pesticides and other chemicals of emerging concern (CECs). This requires screening analysis with high confidence for these compounds and their metabolites in complex matrices, which is hampered by the fact that no reference standards are available for most metabolites. We address this challenge by a high-throughput workflow based on incubation of pesticides (or other CECs) with human liver S9, followed by solid-phase extraction, liquid chromatography−high-resolution mass spectrometry (LC−HRMS) analysis, and automated data processing to generate a database (retention time, precursor m/z, and MS 2 spectral library) for the annotation in human samples. The metabolite prioritization consists of statistical comparisons and mass defect and m/z range filtering to obtain a subset of probable phase I metabolites, for which molecular formulas and likely metabolic transformation are retrieved. We tested the workflow on 22 pesticides, for which we could determine 91 metabolite molecular formulas which are only partly covered by the literature and/or predicted by in silico metabolization. Our workflow allows for an efficient generation of metabolite reference information, which can be used directly for annotating LC−HRMS data from human samples. A full structure elucidation of individual metabolites can be limited to those being actually present in human samples.

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Suspect and untargeted screening of bisphenol S metabolites produced by in vitro human liver metabolism

Cited by 19 publications

References 36 publications

In Vitro Metabolism of Five Bisphenol A Analogs Studied by LC-HRMS/MS

In Vitro Metabolism of Five Bisphenol A Analogs Studied by LC-HRMS/MS

Retrieving and Utilizing Hypothetical Neutral Losses from Tandem Mass Spectra for Spectral Similarity Analysis and Unknown Metabolite Annotation

Improving the Screening Analysis of Pesticide Metabolites in Human Biomonitoring by Combining High-Throughput In Vitro Incubation and Automated LC–HRMS Data Processing

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