Analysis of nerve agent metabolites from nail clippings by liquid chromatography tandem mass spectrometry

Abstract

While several methods for the bioanalysis of nerve agents or their metabolites have been developed for the verification of nerve agent exposure, these methods are generally limited in the amount of time after an exposure that markers of exposure can be detected (due to rapid metabolism from biological matrices). In this study, a method for the analysis of nerve agent hydrolysis products from nail clippings was developed to allow evaluation of nails as a long-term repository of these markers. Pinacolyl methylphosphonic acid (PMPA) and isopropyl methylphosphonic acid (IMPA) were extracted from nail samples with N,N-dimethylformamide and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Limits of detection for PMPA and IMPA were 0.3μg/kg and 7.5μg/kg and linear ranges were 0.75-300μg/kg and 30-1500μg/kg, respectively. Precision was within 10% and 8% for PMPA and IMPA, respectively, and accuracy was 100±12% for both analytes. The approach presented here is complementary to current methods for nerve agent exposure verification, and should allow for long-term determination of nerve agent poisoning.

Poisoning with Soman, an Organophosphorus Nerve Agent, Alters Fecal Bacterial Biota and Urine Metabolites: a Case for Novel Signatures for Asymptomatic Nerve Agent Exposure

“…Current clinical nerve agent exposure assessments are primarily based on overt physiological reactions such as convulsions, loss of consciousness, and salivation for high-dose exposures or pupil constriction and respiratory distress for low-dose exposures (12,13). Recent studies have also demonstrated the feasibility of identifying OP hydrolysis products in hair and nail clippings to verify nerve agent exposure after 30 days (13,14). Hence, monitoring asymptomatic exposure or verifying suspected exposure during the presymptomatic phase using minimally invasive and rapid molecular methods represents an ideal approach and capability.…”

Essential Lessons in a Potential Sarin Attack Disaster Plan for a Resource-Constrained Environment

“…Although a number of methods are available to accurately test for the presence of sarin in fingernail and hair samples, real-time field testing remains elusive. 56,57 There are, however, a number of current scientific projects aimed at using nanotechnology and lab-on-a-chip technology to test fingerprick blood samples for the presence of organophosphate compounds in the bloodstream. 24,[54][55][56][57][58][59][60][61][62][63] Portable handheld devices that can quickly detect and accurately measure various chemical warfare agents, even in the gaseous form, are currently under development.…”

Toxic effects and bioaccumulation of pinacolyl methylphosphonate acid in zebrafish following soman exposure to a water environment

“…For the verication of nerve agent exposure, hair, nail, blood, and urine samples were assessed for the detection of PMPA and other nerve agent hydrolysis products by LC-MS/MS, and the limits of detection (LODs) for PMPA were found to be 0.15 mg kg −1 , 0.3 mg kg −1 , 1.0 ng mL −1 , and 0.03 ng mL −1 , respectively. [18][19][20][21] For monitoring their degree and site of contamination in the environment, tap water and soil samples were assessed for the detection of PMPA and other nerve agent hydrolysis products, and the limits of detection (LODs) for PMPA were found to be 0.01 ng mL −1 and 1.0 ng g −1 . 22,23 Zebrash (Danio rerio) is a small tropical freshwater bony sh, in which the genes of zebrash are highly similar to human genes.…”