High throughput quantitative analysis of the β-lyase sulfur mustard metabolite, 1,1′-sulfonylbis[2-(methylsulfinyl)ethane] in urine via high performance liquid chromatography tandem mass spectrometry

Bevan, Martin J.; Wogen, M. T.; Lunda, Mark D.; Saravia, Stefan

doi:10.1016/j.jchromb.2017.02.030

Cited by 12 publications

(4 citation statements)

References 17 publications

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“…[5][6][7][8][9][10] However, the methods for analysing protein and DNA adducts of NMs are preferable as they are stable from several weeks to months after exposure. 11,12 For sulphur mustard (SM), several methods were developed to determine β-lyase metabolites [13][14][15][16][17] for urine samples. Therefore, one option to detect NMs in biomedical samples is to study their conjugation with GSH.…”

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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Section: Introductionmentioning

confidence: 99%

Glutathione conjugation of nitrogen mustards: In vitro study

Hamzah

Kjellberg

Vanninen

2023

Rapid Comm Mass Spectrometry

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“…11 After the HD exposure, the metabolic pathways in rats or humans have been thoroughly studied and reviewed. 12 It has been determined that hydrolysis, involving the replacement of chlorine atoms by hydroxy groups and reactions with nucleophilic groups, is the primary pathway when HD is exposed to the human body. 13 Various adducts can be detected in the blood samples collected from the individuals affected in the exposure, including DNA adducts or protein adducts.…”

Section: Introductionmentioning

confidence: 99%

“…After the HD exposure, the metabolic pathways in rats or humans have been thoroughly studied and reviewed . It has been determined that hydrolysis, involving the replacement of chlorine atoms by hydroxy groups and reactions with nucleophilic groups, is the primary pathway when HD is exposed to the human body .…”

Section: Introductionmentioning

confidence: 99%

“…It has been determined that hydrolysis, involving the replacement of chlorine atoms by hydroxy groups and reactions with nucleophilic groups, is the primary pathway when HD is exposed to the human body . Various adducts can be detected in the blood samples collected from the individuals affected in the exposure, including DNA adducts or protein adducts. – The main urinary metabolites after the HD exposure were identified to be thiodiglycol (TDG) and other hydrolysis products [Figure ]. – The presence of these metabolic products or adducts can serve as biomarkers for retrospectively detection …”

Section: Introductionmentioning

confidence: 99%

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Simultaneous Quantification of Biomarkers for Bis-(2-chloroethyl) Sulfide and 1,2-Bis(2-chloroethylthio) Ethane Exposure in Human Urine at Trace Exposure Levels by Gas Chromatography Tandem Mass Spectrometry via Simultaneous Incubation and Extraction

Li,

Yang,

Yan

et al. 2023

Chem. Res. Toxicol.

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Sulfur mustard [HD; sulfide] and other analogues are a kind of highly toxic vesicant and have been prohibited by the Organization for the Prohibition of Chemical Weapons (OPCW) since 1997. Exposures to HD could generate several adducts in the plasma and hydrolysis products in the urine, which are widely applied as biomarkers to identify HD exposure in forensic analysis. Several methods have been developed for the detection of related biomarkers. However, most methods are based on complex derivatization, and not enough attention is paid to HD analogues. A modified and convenient analytical method reported herein includes simultaneous incubation and organic solvent extraction. The biomarkers such as thiodiglycol and 1,2-bis (2-hydroxyethylthio) are transferred to HD and 1,2-bis(2-chloroethylthio) ethane via hydrochloric acid at the appropriate temperature. The analytes are analyzed by gas chromatography tandem mass spectrometry (GC−MS/MS) with 2-chloroethyl ethyl sulfide (2-CEES) applied as the internal standard. The interday and intraday study according to FDA rules has been achieved to evaluate the accuracy and precision of the method. The two targets are detected with a good linearity (R 2 > 0.99) in the concentration ranges from 5 to 1000 ng/mL and 10 to 1000 ng/mL, with small relative standard deviations (RSD ≤6.62% and RSD ≤6.93%) and favorable recoveries between 90.3 and 107.3% and between 89.4 and 108.7%, respectively. The established method can be used for retrospective detection of sulfur mustards in biological samples and successfully applied in the biomedical proficiency testing organized by the OPCW.

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