Impurity Profiling to Match a Nerve Agent to Its Precursor Source for Chemical Forensics Applications

Fraga, Carlos G.; Acosta, Gabriel A. Pérez; Crenshaw, M.; Wallace, Krys; Mong, Gary M.; Colburn, Heather A.

doi:10.1021/ac202340u

Cited by 52 publications

(29 citation statements)

References 28 publications

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“…In addition, in a number of samples (hair, skin), DIMP (Fig. 1 , 6th line), one of the most common contaminants formed during production of sarin [ 18 ], was detected by LC–ESI(+)-MS/MS MRM and LC–ESI(+)-HR-MS (Figs. 2 , 4 f).…”

Section: Resultsmentioning

confidence: 99%

Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network

John¹,

Schans

Koller³

et al. 2017

Forensic Toxicol

191

121

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During the United Nations fact-finding mission to investigate the alleged use of chemical warfare agents in the Syrian Arab Republic in 2013, numerous tissues from a deceased female victim, who had displayed symptoms of cholinergic crisis, were collected. The Organisation for the Prohibition of Chemical Weapons (OPCW) authorized two specialized laboratories in the Netherlands and Germany for forensic analysis of these samples. Diverse modern mass spectrometry (MS)-based procedures in combination with either liquid chromatography (LC) or gas chromatography (GC) separation were applied. A variety of biotransformation products of the nerve agent sarin was detected, including the hydrolysis product O-isopropyl methylphosphonic acid (IMPA) as well as covalent protein adducts with e.g., albumin and human butyrylcholinesterase (hBChE). IMPA was extracted after sample acidification by solid-phase extraction and directly analyzed by LC–tandem-MS with negative electrospray ionization (ESI). Protein adducts were found, either by fluoride-induced reactivation applying GC–MS techniques or by LC–MS-based detection after positive ESI for proteolyzed proteins yielding phosphonylated tyrosine residues or a specific phosphonylated hBChE-derived nonapeptide. These experimental results provided unambiguous evidence for a systemic intoxication and were the first proving the use of sarin in the ongoing bellicose conflict. This scenario underlines the requirement for qualified and specialized analytical laboratories to face repeated violation of the Chemical Weapons Convention.

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Section: Resultsmentioning

confidence: 99%

Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network

John¹,

Schans

Koller³

et al. 2017

Forensic Toxicol

191

121

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“…[8] Like strychnine, many compounds of interest in chemical forensics are acids or bases with known stable cation or anion salts of their neutral form (for example: some natural products and many pesticides, pharmaceuticals, and products of illicit chemical synthesis). The counterion is an intrinsic component of such samples and is not easily separated from the compound of interest except by acid-base extraction or an ion exchange process.…”

Section: Introductionmentioning

confidence: 99%

Counterion influence on chemical shifts in strychnine salts

Metaxas

Cort

2013

Magnetic Reson in Chemistry

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The highly toxic plant alkaloid strychnine is often isolated in the form of the anion salt of its protonated tertiary amine. Here, we characterize the relative influence of different counterions on (1)H and (13)C chemical shifts in several strychnine salts in D2O, methanol-d4 (CD3OD), and chloroform-d (CDCl3) solvents. In organic solvents but not in water, substantial variation in chemical shifts of protons near the tertiary amine was observed among different salts. These secondary shifts reveal differences in the way each anion influences electronic structure within the protonated amine. The distributions of secondary shifts allow salts to be easily distinguished from each other as well as from the free base form. Slight concentration dependence in chemical shifts of some protons near the amine was observed for two salts in CDCl3, but this effect is small compared with the influence of the counterion. Distinct chemical shifts in different salt forms of the same compound may be useful as chemical forensic signatures for source attribution and sample matching of alkaloids such as strychnine and possibly other organic acid and base salts.

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“…In brief, XCMS identifies features whose relative intensity varies between sample groups and calculates p-values as well as fold changes. The software has been used for a wide range of applications, including bud and fruit developments in plants 7-9 , cancer research 10-14 , chronic pain 15 , pathogenesis of hepatitis B 16 , forensics 17,18 , long-term studies of human serum 19 , pregnancy-specific syndromes 20 , and stem cell differentiation 21 . XCMS is distributed as an R package and is operated through a command-line interface or customized scripts, making it flexible and particularly suitable for batch-processing.…”

mentioning

confidence: 99%

XCMS Online: A Web-Based Platform to Process Untargeted Metabolomic Data

Tautenhahn¹,

Patti²,

Rinehart³

et al. 2012

Anal. Chem.

1,140

865

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Recently, interest in untargeted metabolomics has become prevalent in the general scientific community among an increasing number of investigators. The majority of these investigators, however, do not have the bioinformatic expertise that has been required to process metabolomic data by using command-line driven software programs. Here we introduce a platform to process untargeted metabolomic data that uses an intuitive graphical interface and does not require installation or technical expertise. This platform, called XCMS Online, is a web-based version of the widely used XCMS software that allows users to easily upload and process liquid chromatography/mass spectrometry data with only a few mouse clicks. XCMS Online provides a solution for the complete untargeted metabolomic workflow including feature detection, retention time correction, alignment, annotation, statistical analysis, and data visualization. Results can be browsed online in an interactive, customizable table showing statistics, chromatograms, and putative METLIN identities for each metabolite. Additionally, all results and images can be downloaded as zip files for offline analysis and publication. XCMS Online is available at https://xcmsonline.scripps.edu.

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Impurity Profiling to Match a Nerve Agent to Its Precursor Source for Chemical Forensics Applications

Cited by 52 publications

References 28 publications

Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network

Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network

Counterion influence on chemical shifts in strychnine salts

XCMS Online: A Web-Based Platform to Process Untargeted Metabolomic Data

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