Applying human and pig hepatic <i>in vitro</i> experiments for sulfur mustard study: Screening and identification of metabolites by liquid chromatography/tandem mass spectrometry

Halme, Mia; Pesonen, Maija; Hakala, Ullastiina; Pasanen, Markku; Vähäkangas, Kirsi; Vanninen, Paula

doi:10.1002/rcm.7218

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…The Orbitrap‐ESI‐MS/MS spectrum and plausible interpretation of the entire HDSO fragmentation are shown in Figure 2. The MS/MS spectrum of HDSO along with proposed ion structures have been described by Halme et al 36 The high mass low abundant ion at m/z 146.9436 was probably formed after elimination of ethylene. This low intensity product ion at m/z 146.9436 was sequentially fragmented by QTRAP‐MS 3 and resulted in the formation of a product ion at m/z 110.9968 (loss of hydrogen chloride).…”

Section: Resultsmentioning

confidence: 73%

A novel approach for the detection and identification of sulfur mustard using liquid chromatography–electrospray ionization–tandem mass spectrometry based on its selective oxidation to sulfur mustard monoxide with N‐iodosuccinimide

et al. 2021

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A new derivatization strategy for the detection and identification of sulfur mustard (HD) via liquid chromatography–electrospray ionization–tandem mass spectrometry (LC‐ESI‐MS/MS) is developed. The method incorporates selective oxidation of the sulfide group by the electrophilic iodine reagent N‐iodosuccinimide (NIS) to produce sulfur mustard monoxide (HDSO). The derivatization reaction efficiencies were evaluated with acetonitrile extracts of soil, asphalt, cloth, Formica, and linoleum spiked with HD at concentrations of 50–5000 pg/ml and found to be similar to that with pure acetonitrile. The current derivatization approach is the first to preserve the identity of chloride groups and support HD regulation and evidentiary findings.

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Section: Resultsmentioning

confidence: 73%

A novel approach for the detection and identification of sulfur mustard using liquid chromatography–electrospray ionization–tandem mass spectrometry based on its selective oxidation to sulfur mustard monoxide with N‐iodosuccinimide

et al. 2021

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“…Increased bilirubin could be a direct result of toxic effects of SM on the liver. The hepatic metabolism of SM has been reported in the literature (Black and Read, ; Jafari, ; Halme et al ., ) and radiometric data from this study provide further evidence that 14 C–SM or radiolabelled metabolites of SM are associated with the liver. Furthermore, decontamination with WoundStat™ significantly decreased the amount of radiolabelled 14 C detected in the liver, which is consistent with the absence of increased skin absorption at ~420 nm in this group.…”

Section: Discussionmentioning

confidence: 97%

The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

Hall

Lydon

Dalton³

et al. 2017

J of Applied Toxicology

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This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for decontamination of superficial (non-haemorrhaging), sulphur mustard-contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled physical damage and exposed to 10 μL C-radiolabelled sulphur mustard ( C-SM). Animals were randomly assigned to either a control or a treatment group. In the latter, WoundStat™ was applied 30 s post exposure and left in situ for 1 h. Skin lesion progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements. Skin, blood and organ samples were taken post mortem for histopathological assessment, C-SM distribution and toxicokinetic analyses. Application of SM to damaged skin without decontamination was rapidly followed by advanced signs of toxicity, including ulceration and decreased blood flow at the exposure site in all animals. WoundStat™ prevented ulceration and improved blood flow at the exposure site in all decontaminated animals (n = 6). Furthermore, significantly smaller quantities of C-SM were detected in the blood (45% reduction), and recovered from skin (70% reduction) and skin surface swabs (99% reduction) at 6 h post-challenge. Overall, the distribution of C-SM in the internal organs was similar for both groups, with the greatest concentration in the kidneys, followed by the liver and small intestine. WoundStat™ significantly reduced the amount of C-SM recovered from the liver, a key organ for SM metabolism and detoxification. This study demonstrates that WoundStat™ is a suitable product for reducing the ingress and toxicity of a chemical warfare agent. Copyright © 2017 John Wiley & Sons, Ltd.

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“…NMs-GSH conjugates exhibited the same pattern of fragmentation as previously observed. 25 The list of product ions together with their masses and ion losses for all conjugates are presented in Table 4.…”

Section: Conjugate Confirmationmentioning

confidence: 99%

“…An in vitro investigation was conducted, and the S9 fraction liver homogenate was used since it contains both microsomal and cytosolic fractions. 25 That study was performed with a reaction mixture containing S9 fraction liver homogenate, nicotinamide adenine dinucleotide phosphate (NADPH), GSH and phosphate buffer to create physiological pH conditions. The S9 fraction liver homogenate contains phase I and phase II metabolic enzymes.…”

Section: Introductionmentioning

confidence: 99%

Glutathione conjugation of nitrogen mustards: In vitro study

Hamzah

Kjellberg

Vanninen

2023

Rapid Comm Mass Spectrometry

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Rationale: This paper describes an in vitro study designed to identify metabolic biomarkers resulting from the conjugation of nitrogen mustards (NMs) with glutathione (GSH). The method developed is essential in providing evidence in the event of NM exposure in biomedical samples.Methods: The mass spectral characterization of the proposed NMs-GSH conjugates was performed with liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). The final reaction mixtures were analysed in positive electrospray ionisation (ESI) at different incubation times.Results: This study identified three types of conjugates in addition to ethanolamines, the hydrolysis products of NMs. Monoglutathionyl, diglutathionyl and phosphorylated conjugates were produced for each of the NMs, bis(2-chloroethyl) ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2) and tris(2-chloroethyl)amine (HN3). The monoglutathionyl conjugates consisted of HN1-GSH, HN2-GSH and HN3-GSH. The spontaneous and primary conjugates of diglutathionyl were HN1-GSH2, HN2-GSH2 and HN3-GSH2. These included phosphorylated conjugates, namely HN1-GSH-PO 4 , HN2-GSH-PO 4 and HN3-GSH-PO 4 , as might have formed due to hydrolysis in phosphate buffer. Conclusions:The mass spectral data of all conjugates formed in the presence of all NMs and GSH are reported in this study. These GSH metabolites can be used to confirm NMs toxicity in biological samples such as urine.

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Applying human and pig hepatic in vitro experiments for sulfur mustard study: Screening and identification of metabolites by liquid chromatography/tandem mass spectrometry

Cited by 8 publications

References 26 publications

A novel approach for the detection and identification of sulfur mustard using liquid chromatography–electrospray ionization–tandem mass spectrometry based on its selective oxidation to sulfur mustard monoxide with N‐iodosuccinimide

A novel approach for the detection and identification of sulfur mustard using liquid chromatography–electrospray ionization–tandem mass spectrometry based on its selective oxidation to sulfur mustard monoxide with N‐iodosuccinimide

The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

Glutathione conjugation of nitrogen mustards: In vitro study

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