Highly Accurate Detection and Identification Methodology of Xenobiotic Metabolites Using Stable Isotope Labeling, Data Mining Techniques, and Time-Dependent Profiling Based on LC/HRMS/MS

Takahashi, Masatomo; Izumi, Yoshihiro; Iwahashi, Fukumatsu; Nakayama, Yasumune; Iwakoshi, Mitsuhiko; Nakao, Motonao; Yamato, Seiji; Fukusaki, Eiichiro; Bamba, Takeshi

doi:10.1021/acs.analchem.8b01388

Cited by 25 publications

(21 citation statements)

References 31 publications

(72 reference statements)

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“…Compound discoverer 3.0 software (Thermo Fisher Scientific) was used for data processing, involving peak alignment, peak detection, background subtraction, data grouping, and filling gaps with volcano plots. 31 Details on the data processing parameters used are shown in Table S3. The paired-peak filtering (PPF) technique for detecting significant compounds between unlabeled acrylamide-added and 13 C 3 -acrylamide-added samples was developed by Takahashi and co-workers.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The paired-peak filtering (PPF) technique for detecting significant compounds between unlabeled acrylamide-added and 13 C 3 -acrylamide-added samples was developed by Takahashi and co-workers. 31 PPF is a technique that can detect unlabeled and 13 C 3 -labeled pairs of acrylamide adducts with high accuracy, without detecting false positive peaks derived from solvents, matrices, or noise. Pairs of adducts derived from unlabeled acrylamide and 13 C 3 -labeled acrylamide were identified using the following parameters: (i) the difference in the m/z value, dependent on the number of labels and the difference in mass of the labeled isotope element of 3.0102 (Δm/z = 1.0034 × 3), (ii) the mass error tolerance of 5 ppm, and (iii) the Δ in retention time (RT) of 0.1 min.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…In order to search for unknown metabolites, our group previously developed a structural estimation technology using ultra-high performance liquid chromatography high-resolution mass spectrometry (UHPLC/HRMS) and UHPLC highresolution tandem mass spectrometry (UHPLC/HRMS/MS) to determine the composition formulae of the relevant substances from the exact mass of unlabeled and stable isotopically labeled compounds. 31 In this study, this technique is applied to identify acrylamide adducts in canned milk coffee stored for a long time and containing acrylamide and 13 C 3acrylamide. Identification of these substances could provide new insights into methods of reduction of acrylamide in coffee beverages, which were not yet obvious.…”

Section: ■ Introductionmentioning

confidence: 99%

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Identification of Acrylamide Adducts Generated during Storage of Canned Milk Coffee

Yoshioka

Izumi

Takahashi

et al. 2020

J. Agric. Food Chem.

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Since coffee is a significant contributor to the consumption of acrylamide, its reduction is required. Acrylamide is produced during the roasting of coffee beans, but the roasting process is an essential step in determining the taste of coffee. Acrylamide content in coffee has been suggested to decrease by reacting with proteins and/or other substances during storage, but details are unknown. Investigation of acrylamide adducts may contribute to a strategy for acrylamide reduction in coffee. In this study, a stable isotope labeling technique, combined with high-resolution mass spectrometry, allows the identification of acrylamide adducts (3-hydroxypyridine-acrylamide and pyridine-acrylamide) in canned milk coffee. Other acrylamide adducts derived from milk coffee proteins, Lys-acrylic acid and CysSO2-acrylic acid, were identified. During a 4-month storage period, the formation of these four adducts was found to reduce the total content of acrylamide by 75.3% in canned milk coffee. Therefore, endogenous proteins can be used in acrylamide reduction.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Acrylamide Adducts Generated during Storage of Canned Milk Coffee

Yoshioka

Izumi

Takahashi

et al. 2020

J. Agric. Food Chem.

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“…The subsequent analysis of too many suspected features is an extremely time-consuming task. , Stable isotope labeling (SIL), i.e. introducing deuterated atoms or C 13 atoms into the parent compounds, has been proposed to provide additional structural information to exclude interfering species. ,− However, the isotopically labeled reagents are usually expensive and difficult to synthesize, which greatly constrains application of the SIL method. Therefore, the development of alternative methods that seek new structural characteristics for differentiating the metabolites from interfering species is still needed.…”

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confidence: 99%

Noncovalently Tagged Gas Phase Complex Ions for Screening Unknown Contaminant Metabolites in Plants

et al. 2021

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Screening the metabolites of emerging organic contaminants (EOCs) from complicated biological matrices is an important but challenging task. Although stable isotope labeling (SIL) is frequently used to facilitate the identification of contaminant metabolites from redundant interfering components, the isotopically labeled reagents are expensive and difficult to synthesize, which greatly constrains the application of the SIL method. Herein, a new online noncovalent tagging method was developed for screening the metabolites of 1H-benzotriazol (BT) based on the characteristic structural moieties reserved in the metabolites. By selecting β-cyclodextrin (β-CD) as a macrocyclic tagging reagent, metabolites with the reserved moiety were expected to exhibit a characteristic shift of the mass-to-charge ratio (Δm/z = 1134.3698) after being noncovalently tagged by β-CD. Based on the characteristic mass shift, the suspected features were reduced by 1 order of magnitude, as numerous interfering species that could not be effectively tagged by β-CD were excluded. From these suspected features, two metabolites of BT that have not been reported before were successfully screened out. The significant characteristic mass shift caused by the noncovalent tagging method is easier to identify with more confidence than the previously reported SIL method. Besides, noncovalent tagging reagents can be much more accessible and less expensive than isotopically labeled reagents. Hence, this online noncovalent tagging method can be an intriguing alternative to the conventional SIL method.

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Efficient lipidomic approach for the discovery of lipid ligands for immune receptors by combining LC-HRMS/MS analysis with fractionation and reporter cell assay

Tomiyasu,

Takahashi,

Toyonaga

et al. 2023

Anal Bioanal Chem

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C-type lectin receptors (CLRs), which are pattern recognition receptors responsible for triggering innate immune responses, recognize damaged self-components and immunostimulatory lipids from pathogenic bacteria; however, several of their ligands remain unknown. Here, we propose a new analytical platform combining liquid chromatography-high-resolution tandem mass spectrometry with microfractionation capability (LC-FRC-HRMS/MS) and a reporter cell assay for sensitive activity measurements to develop an efficient methodology for searching for lipid ligands of CLR from microbial trace samples (crude cell extracts of approximately 5 mg dry cell/mL). We also developed an in-house lipidomic library containing accurate mass and fragmentation patterns of more than 10,000 lipid molecules predicted in silico for 90 lipid subclasses and 35 acyl side chain fatty acids. Using the developed LC-FRC-HRMS/MS system, the lipid extracts of Helicobacter pylori were separated and fractionated, and HRMS and HRMS/MS spectra were obtained simultaneously. The fractionated lipid extract samples in 96-well plates were thereafter subjected to reporter cell assays using nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing mouse or human macrophage-inducible C-type lectin (Mincle). A total of 102 lipid molecules from all fractions were annotated using an in-house lipidomic library. Furthermore, a fraction that exhibited significant activity in the NFAT-GFP reporter cell assay contained α-cholesteryl glucoside, a type of glycolipid, which was successfully identified as a lipid ligand molecule for Mincle. Our analytical platform has the potential to be a useful tool for efficient discovery of lipid ligands for immunoreceptors. Graphical Abstract

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Highly Accurate Detection and Identification Methodology of Xenobiotic Metabolites Using Stable Isotope Labeling, Data Mining Techniques, and Time-Dependent Profiling Based on LC/HRMS/MS

Cited by 25 publications

References 31 publications

Identification of Acrylamide Adducts Generated during Storage of Canned Milk Coffee

Identification of Acrylamide Adducts Generated during Storage of Canned Milk Coffee

Noncovalently Tagged Gas Phase Complex Ions for Screening Unknown Contaminant Metabolites in Plants

Efficient lipidomic approach for the discovery of lipid ligands for immune receptors by combining LC-HRMS/MS analysis with fractionation and reporter cell assay

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