Simultaneous determination of sulfur mustard and related oxidation products by isotope-dilution LC–MS/MS method coupled with a chemical conversion

Qi, Meiling; Xu, Bin; Wu, Jianfeng; Zhang, Yajiao; Zong, Cheng; Chen, Jia; Guo, Lei; Xie, Jianwei

doi:10.1016/j.jchromb.2016.06.003

Cited by 14 publications

(8 citation statements)

References 24 publications

(32 reference statements)

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“…< Figure 1> A first proposed approach for biomonitoring of exposure to SM involved quantification of the direct oxidation product of SM, bis-chloroethyl sulfoxide (SMO). Rapid, simple and quantitative analytical methods were developed for this early SM biomarker present in blood for a rapid diagnostic during the asymptomatic latency period (less than 12h) [13,14]. The directly hydrolyzed metabolite thiodiglycol (TDG) was detected in urine from SM-treated rats for 48h [15].…”

Section: Introductionmentioning

confidence: 99%

Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog

et al. 2021

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Sulfur mustard (SM), a chemical warfare agent, is a strong alkylating compound that readily reacts with numerous biomolecules. The goal of the present work was to define and validate new biomarkers of exposure to SM that could be easily accessible in urine or plasma. Because investigations using SM are prohibited by the Organization for the Prohibition of Chemical Weapons, we worked with 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of SM. We developed an ultra-high-pressure liquid chromatography -tandem mass spectrometry approach (UHPLC-MS/MS) to the conjugate of CEES to glutathione and two of its metabolites, the cysteine and the N-acetyl-cysteine conjugates. The N7guanine adduct of CEES (N7Gua-CEES) was also targeted. After synthesizing the specific biomarkers, a solid phase extraction protocol and a UHPLC-MS/MS method with isotopic dilution were optimized.We were able to quantify N7Gua-CEES in the DNA of HaCaT keratinocytes and of explants of human skin exposed to CEES. N7Gua-CEES was also detected in the culture medium of these two models, together with the glutathione and the cysteine conjugates. In contrast, the N-acetyl-cysteine conjugate was not detected. The method was then applied to plasma from mice cutaneously exposed to CEES.All four markers could be detected. Our present results thus validate both the analytical technique and the biological relevance of new, easily quantifiable biomarkers of exposure to CEES. Because CEES behaves very similarly to SM, the results are promising for application to this toxic of interest.

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Section: Introductionmentioning

confidence: 99%

Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog

et al. 2021

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“…This is the reason why quantification of exposure and effect biomarkers represent an interesting complementary approach. Evidence that SM and its analogs diffuse in the blood stream is shown by the detection of its degradation products (Li et al, 2013;Manandhar et al, 2018;Qi et al, 2016) and of protein adducts in plasma (John et al, 2019;Liu et al, 2015;Noort et al, 2008;Xu et al, 2014). SM or CEES may also react in plasma with small molecules such as glutathione, which leads to the presence of conjugates in blood.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the systemic diffusion of (2-chloroethyl)-ethyl-sulfide, a sulfur mustard analog, and its deleterious effects in brain

Gilardoni

Léonço

Caffin³

et al. 2021

Toxicology

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Sulfur mustard, a chemical warfare agent known to be a vesicant of skin, readily diffuses in the blood stream and reaches internal organs. In the present study, we used the analog (2chloroethyl)-ethyl-sulfide (CEES) to provide novel data on the systemic diffusion of vesicants and on their ability to induce brain damage, which result in neurological disorders. SKH-1 hairless mice were topically exposed to CEES and sacrificed at different time until 14 days after exposure. A plasma metabolomics study showed a strong systemic impact following a self-protection mechanism to alleviate the injury of CEES exposure. This result was confirmed by the quantification of specific biomarkers in plasma. Those were the conjugates of CEES with glutathione (GSH-CEES), cysteine (Cys-CEES) and N-acetyl-cysteine (NAC-CEES), as well as the guanine adduct (N7Gua-CEES). In brain, N7Gua-CEES could be detected both in DNA and in organ extracts. Similarly, GSH-CEES, Cys-CEES and NAC-CEES were present in the extracts until day14. Altogether, these results, based on novel exposure markers, confirm the ability of vesicants to induce internal damage following dermal exposure. The observation of alkylation damage to glutathione and DNA in brain provides an additional mechanism to the neurological insult of SM.

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“…The direct oxidative metabolite of HD, sulfur mustard monoxide (mustard sulfoxide, HDSO), has received little attention as a potential HD diagnostic marker, likely because most toxicokinetic studies have used urine, and HDSO is only present as a minor urinary metabolite 12,13 . However, unlike TDG and TDGO, HDSO is not endogenous; hence, its presence is definitive evidence of HD exposure 14,15 …”

Section: Introductionmentioning

confidence: 99%

“…12,13 However, unlike TDG and TDGO, HDSO is not endogenous; hence, its presence is definitive evidence of HD exposure. 14,15 In the environment (e.g., soil), sulfur mustard is spontaneously hydrolyzed, mainly to TDG and TDGO. Likewise, in clinical samples, these degradation products do not provide robust evidence to support HD use.…”

mentioning

confidence: 99%

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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Simultaneous determination of sulfur mustard and related oxidation products by isotope-dilution LC–MS/MS method coupled with a chemical conversion

Cited by 14 publications

References 24 publications

Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog

Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog

Evidence for the systemic diffusion of (2-chloroethyl)-ethyl-sulfide, a sulfur mustard analog, and its deleterious effects in brain

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

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