Determination of free G-type nerve agents in blood: in situ derivatization on a dried blood spot (DBS) paper followed by LC–MS/MS analysis

Aviram, Lilach Yishai; Loewenthal, Dan; Weissberg, Avi; Marder, Dana; Gura, Sigalit; Chapman, Shira; Gez, Rellie; Lazar, Shlomi; Dagan, S.

doi:10.1007/s11419-019-00516-8

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…In a previous study [19], we reported the use of DBS for monitoring exposure to OP-CWAs. Here, for the first time, the application of DUS for the identification of CWA metabolites was explored.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we found that the optimized extraction solvent for phosphonic acids in DBS is a mixture of MeOH:TDW (50:50) [19]. Here, during the optimization process, several extraction volumes of this mixture (50, 100, 200, 300 and 500 µL) were evaluated.…”

Section: Development and Optimization Of The Extraction Procedures (U...mentioning

confidence: 99%

“…The details of the LC-MS method were reported previously and are also provided in the Supplementary Materials [19]. Briefly, a targeted analysis was performed using the LC-QQQ instrumentation A (Agilent 1290 LC coupled to a Sciex 5500 Qtrap QQQ-MS), while an untargeted analysis was performed with an LC-HRMS system (Agilent 1290 LC coupled to a Q-Exactive+MS).…”

Section: Instrument Conditionsmentioning

confidence: 99%

“…Because of these advantages, as well as the fact that urine is the preferred matrix for the detection of drugs [14], the incorporation of this technique has accelerated in recent years for toxicology screening [15], metabolite-based comprehensive screening [16], forensic toxicology [17], etc. DBS was explored for the detection of exposure to CWAs, with promising results [18][19][20][21]. Although DUS has not yet been tested in this scenario, it also promises to be highly valuable in cases of large-scale field sampling, such as mass casualty events.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring Exposure to Five Chemical Warfare Agents Using the Dried Urine Spot Technique and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry—In Vivo Determination of Sarin Metabolite in Mice

Yishai Aviram,

Dagan,

Hindi

et al. 2023

Molecules

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Dried urine spot (DUS) is a micro-sample collection technique, known for its advantages in handling, storage and shipping. It also uses only a small volume of urine, an essential consideration in working with small animals, or in acute medical situations. Alkyl-phosphonic acids are the direct and indicative metabolites of organophosphorus chemical warfare agents (OP-CWAs) and are present in blood and urine shortly after exposure. They are therefore crucially important for monitoring casualties in war and terror scenarios. We report here a new approach for the determination of the metabolites of five CWAs in urine using DUS. The method is based on a simple and rapid sample preparation, using only 50 µL of urine, spotted and dried on DBS paper, extracted using 300 µL methanol/water and analyzed via targeted LC-MS/MS. The detection limits for the five CWAs, sarin (GB), soman (GD), cyclosarin (GF), VX and RVX in human urine were from 0.5 to 5 ng/mL. Recoveries of (40–80%) were obtained in the range of 10–300 ng/mL, with a linear response (R2 > 0.964, R > 0.982). The method is highly stable, even with DUS samples stored up to 5 months at room temperature before analysis. It was implemented in a sarin in vivo exposure experiment on mice, applied for the time course determination of isopropyl methylphosphonic acid (IMPA, sarin hydrolysis product) in mice urine. IMPA was detectable even with samples drawn 60 h after the mice’s (IN) exposure to 1 LD50 sarin. This method was also evaluated in a non-targeted screening for multiple potential CWA analogs (LC-Orbitrap HRMS analysis followed by automatic peak detection and library searches). The method developed here is applicable for rapid CWA casualty monitoring.

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Section: Discussionmentioning

confidence: 99%

Section: Development and Optimization Of The Extraction Procedures (U...mentioning

confidence: 99%

Section: Instrument Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Monitoring Exposure to Five Chemical Warfare Agents Using the Dried Urine Spot Technique and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry—In Vivo Determination of Sarin Metabolite in Mice

Yishai Aviram,

Dagan,

Hindi

et al. 2023

Molecules

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“…For the successful determination of intact CWAs in biological media, it is necessary not only to ensure the high sensitivity and selectivity of analysis but also to stop the bioconversion of CWAs in an already taken sample. In 2020, a method for the determination of intact G-type organophosphorus nerve agents (OPNAs) in whole blood was reported [17]. The derivatization of OPNAs with 2-[(dimethylamino)methyl]phenol was carried out in dried blood spots.…”

Section: Unstable Highly Toxic Organic Compoundsmentioning

confidence: 99%

Scopes of Bioanalytical Chromatography–Mass Spectrometry

Savelieva

2021

J Anal Chem

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The areas of application of modern bioanalytical chromatography-mass spectrometry are so extensive that any attempt to systematize them becomes subjective. It would be more correct to say that there is no such area of biology and medicine where chromatography-mass spectrometry would not find application. This article focuses on the areas of application of this technique that are either relatively new or insufficiently covered in recent reviews. State-of-the-art bioanalytical techniques have become multitargeted in terms of analytes and standardized in terms of matrices. The ability to detect trace concentrations of analytes in the presence of a huge number of biomatrix macrocomponents using chromatography-mass spectrometry is especially important for bioanalytical chemistry. In the target-oriented determination of persistent organic pollutants by chromatography-mass spectrometry, the main problem is the expansion of the list of analytes, including isomers. In the detection of exposures to unstable toxicants, the fragmented adducts of xenobiotics with biomolecules become target biomarkers along with hydrolytic metabolites. The exposome reflects the general exposure of a human being to total xenobiotics and the metabolic status reflects the physiological state of the body. Chromatography-mass spectrometry is a key technique in metabolomics. Metabolomics is currently used to solve the problems of clinical diagnostics and anti-doping control. Biological sample preparation procedures for instrumental analysis are being simplified and developed toward increasing versatility. Proteomic technologies with the use of various versions of mass spectrometry have found application in the development of new methods for diagnosing coronavirus infections.

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Enantioselective in-vitro elimination kinetics of nerve agents in blood monitored by derivatization and LC–MS/MS analysis

2020

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Determination of free G-type nerve agents in blood: in situ derivatization on a dried blood spot (DBS) paper followed by LC–MS/MS analysis

Cited by 8 publications

References 43 publications

Monitoring Exposure to Five Chemical Warfare Agents Using the Dried Urine Spot Technique and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry—In Vivo Determination of Sarin Metabolite in Mice

Monitoring Exposure to Five Chemical Warfare Agents Using the Dried Urine Spot Technique and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry—In Vivo Determination of Sarin Metabolite in Mice

Scopes of Bioanalytical Chromatography–Mass Spectrometry

Enantioselective in-vitro elimination kinetics of nerve agents in blood monitored by derivatization and LC–MS/MS analysis

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