A quantitative method to detect human exposure to sulfur and nitrogen mustards via protein adducts

Pantazides, Brooke G.; Quiñones-González, Jennifer; Nazario, Danisha M. Rivera; Crow, Brian S.; Perez, Jonas W.; Blake, Thomas A.; Johnson, Rudolph C.

doi:10.1016/j.jchromb.2019.05.005

Cited by 16 publications

(5 citation statements)

References 24 publications

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“…For the retrospective detection of NM biomarkers in plasma, the sample preparation typically involves protein precipitation and selective enzymolysis. 19 However, the whole running process is particular time-consuming and results in a high target loss. In contrast, the monitoring of urinary biomarkers has been demonstrated to be practical and effective, 20 and is more convenient.…”

Section: Introductionmentioning

confidence: 99%

Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine via gas chromatography tandem mass spectrometry

Yang,

Yan

et al. 2023

RSC Adv.

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Section: Introductionmentioning

confidence: 99%

Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine via gas chromatography tandem mass spectrometry

Yang,

Yan

et al. 2023

RSC Adv.

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“…Studies of other degradation products, such as their N‐oxides or piperazinium salts, 25,26 and their determination in decontamination solutions 27 in the human body via protein adducts 28 were also introduced. In addition, an LC/MS/MS method to detect NM degradation products after pentafluorobenzoylation was also recently reported 24 …”

Section: Introductionmentioning

confidence: 99%

Ethanolysis of nitrogen mustards: A novel strategy for nitrogen mustard identification in environmental matrices by liquid chromatography–electrospray ionization–tandem mass spectrometry

Belay,

Shifrovitch,

Prihed

et al. 2024

Rapid Comm Mass Spectrometry

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RationaleNitrogen mustards (NMs) are blistering chemical warfare agents. The ability to detect NMs in environmental samples is very important for obtaining forensic evidence. The most common analytical techniques for NM detection are gas chromatography–mass spectrometry, which detects NMs in their intact form but is disadvantaged by high limits of detection (LODs), and liquid chromatography–electrospray ionization–tandem mass spectrometry (LC/ESI‐MS/MS) of their hydrolysis products, which do not provide robust evidence to support NM use.MethodsWe developed a novel approach to detect and identify NMs using LC/ESI‐MS/MS after chemical derivatization. The method is based on ethoxide‐promoted ethanolysis prior to analysis. The effects of reaction time, temperature, ethoxide concentration and chromatography behavior were studied and optimized. In the developed procedure, 0.1% (v/v) sodium ethoxide solution is added to the NMs in ethanol and agitated for 2 h at 50°C, followed by LC/ESI‐MS/MS, without any other pretreatment.ResultsThe ethanolysis reaction efficiencies were evaluated in ethanolic extracts from soil, asphalt, and ethanol contaminated with 0.5% (v/v) diesel fortified with NMs at a five‐point calibration curve. The calibration curves showed good linearity in the range of 0.05–1 ng/mL, with an R2 value of 0.99, and were similar to those of LC/MS‐grade ethanol, with almost no observable matrix effects. The derivatization products were stable at room temperature, with LODs of 10 pg/mL, in all investigated extracts.ConclusionsThrough this newly developed strategy, the derivatization of active NMs by ethanolysis was achieved for the first time, and these derivatization products can serve as specific indicators for the use and presence of NMs. The methodology can also verify trace levels of NM chemical warfare agents collected in war or terror scenarios in forensic investigations.

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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%

“…Most of the methods for detecting EAs have been developed for the analysis of urine samples 5–10 . 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 13–17 for urine samples.…”

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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A quantitative method to detect human exposure to sulfur and nitrogen mustards via protein adducts

Cited by 16 publications

References 24 publications

Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine via gas chromatography tandem mass spectrometry

Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine via gas chromatography tandem mass spectrometry

Ethanolysis of nitrogen mustards: A novel strategy for nitrogen mustard identification in environmental matrices by liquid chromatography–electrospray ionization–tandem mass spectrometry

Glutathione conjugation of nitrogen mustards: In vitro study

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