title: Quantitation of five organophosphorus nerve agent metabolites in serum using hydrophilic interaction liquid chromatography and tandem mass spectrometry.
abstract: Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman), and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid-phase extraction coupled with high-performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3 to 0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101-105%) and high precision (5-8%) for the detection of these five nerve agent hydrolysis products in serum.
authors.affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy, Atlanta, GA, 30341, USA, ehamelin@cdc.gov.
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Hamelin
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Schulze
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Shaner
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Coleman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lawrence
authors.forename: Brian S
authors.initials: BS
authors.lastname: Crow
authors.forename: E M
authors.initials: EM
authors.lastname: Jakubowski
authors.forename: Rudolph C
authors.initials: RC
authors.lastname: Johnson
mesh_terms: D064751:Ammonium Compounds; D001711:Biotransformation; D002021:Buffers; D002619:Chemical Warfare Agents / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005459:Fluorides; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D057230:Limit of Detection; D009943:Organophosphorus Compounds / Q000097:blood*; D009946:Organothiophosphorus Compounds / Q000097:blood*; D000644:Quaternary Ammonium Compounds; D012524:Sarin / Q000097:blood*; D052616:Solid Phase Extraction; D012999:Soman / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D064751:Ammonium Compounds; D002021:Buffers; D002619:Chemical Warfare Agents; D005459:Fluorides; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D000644:Quaternary Ammonium Compounds; D012524:Sarin; D012999:Soman; C024822:ammonium fluoride; C009680:VX-agent; C053914:cyclohexyl methylphosphonofluoridate