title: Analysis of Nerve Agent Metabolites from Hair for Long-Term Verification of Nerve Agent Exposure.
abstract: Several methods for the bioanalysis of nerve agents or their metabolites have been developed for the verification of nerve agent exposure. However, parent nerve agents and known metabolites are generally rapidly excreted from biological matrixes typically used for analysis (i.e., blood, urine, and tissues), limiting the amount of time after an exposure that verification is feasible. In this study, hair was evaluated as a long-term repository of nerve agent hydrolysis products. Pinacolyl methylphosphonic acid (PMPA; hydrolysis product of soman) and isopropyl methylphosphonic acid (IMPA; hydrolysis product of sarin) were extracted from hair samples with N,N-dimethylformamide and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Limits of detection for PMPA and IMPA were 0.15 μg/kg and 7.5 μg/kg and linear ranges were 0.3-150 μg/kg and 7.5-750 μg/kg, respectively. To evaluate the applicability of the method to verify nerve agent exposure well after the exposure event, rats were exposed to soman, hair was collected after approximately 30 days, and stored for up to 3.5 years prior to initial analysis. PMPA was positively identified in 100% of the soman-exposed rats (N = 8) and was not detected in any of the saline treated animals (N = 6). The hair was reanalyzed 5.5 years after exposure and PMPA was detected in 6 of the 7 (one of the soman-exposed hair samples was completely consumed in the analysis at 3.5 years) rat hair samples (with no PMPA detected in the saline exposed animals). Although analysis of CWA metabolites from hair via this technique is not appropriate as a universal method to determine exposure (i.e., it takes time for the hair to grow above the surface of the skin and typical analysis times are >24 h), it complements existing methods and could become the preferred method for verification of exposure if 10 or more days have elapsed after a suspected exposure.
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University , Avera Health and Science, Box 2202, Brookings, South Dakota 57007, United States.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Appel
authors.affiliation: Pharmacology Branch, Research Division U.S. Army Medical Research Institute of Chemical Defense 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: McDonough
authors.affiliation: Pharmacology Branch, Research Division U.S. Army Medical Research Institute of Chemical Defense 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010, United States.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: McMonagle
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University , Avera Health and Science, Box 2202, Brookings, South Dakota 57007, United States.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Logue
mesh_terms: D002619:Chemical Warfare Agents / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006197:Hair / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057230:Limit of Detection; D000067397:Nerve Agents / Q000032:analysis* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000032:analysis* / Q000378:metabolism; D012524:Sarin / Q000032:analysis / Q000378:metabolism; D012999:Soman / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D002619:Chemical Warfare Agents; D000067397:Nerve Agents; D009943:Organophosphorus Compounds; C048760:isopropyl methylphosphonic acid; C046573:pinacolyl methylphosphonic acid; D012999:Soman; D012524:Sarin