title: A high-throughput UHPLC-MS/MS method for the quantification of five aged butyrylcholinesterase biomarkers from human exposure to organophosphorus nerve agents.
abstract: Organophosphorus nerve agents (OPNAs) are toxic compounds that are classified as prohibited Schedule 1 chemical weapons. In the body, OPNAs bind to butyrylcholinesterase (BChE) to form nerve agent adducts (OPNA-BChE). OPNA-BChE adducts can provide a reliable, long-term protein biomarker for assessing human exposure. A major challenge facing OPNA-BChE detection is hydrolysis (aging), which can continue to occur after a clinical specimen has been collected. During aging, the o-alkyl phosphoester bond hydrolyzes, and the specific identity of the nerve agent is lost. To better identify OPNA exposure events, a high-throughput method for the detection of five aged OPNA-BChE adducts was developed. This is the first diagnostic panel to allow for the simultaneous quantification of any Chemical Weapons Convention Schedule 1 OPNA by measuring the aged adducts methyl phosphonate, ethyl phosphonate, propyl phosphonate, ethyl phosphoryl, phosphoryl and unadducted BChE. The calibration range for all analytes is 2.00-250. ng/mL, which is consistent with similar methodologies used to detect unaged OPNA-BChE adducts. Each analytical run is 3 min, making the time to first unknown results, including calibration curve and quality controls, less than 1 h. Analysis of commercially purchased individual serum samples demonstrated no potential interferences with detection of aged OPNA-BChE adducts, and quantitative measurements of endogenous levels of BChE were similar to those previously reported in other OPNA-BChE adduct assays.
authors: Battelle at the Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Leigh Ann
authors: LA
authors: Graham
authors: Oak Ridge Institute for Science and Education Fellow at the Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Darryl
authors: D
authors: Johnson
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Melissa D
authors: MD
authors: Carter
authors: Oak Ridge Institute for Science and Education Fellow at the Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Emily G
authors: EG
authors: Stout
authors: Oak Ridge Institute for Science and Education Fellow at the Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Huseyin A
authors: HA
authors: Erol
authors: Battelle at the Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Samantha L
authors: SL
authors: Isenberg
authors: Battelle at the Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Thomas P
authors: TP
authors: Mathews
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Jerry D
authors: JD
authors: Thomas
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Rudolph C
authors: RC
authors: Johnson
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D004781:Environmental Exposure / Q000032:analysis; D006207:Half-Life; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D000067397:Nerve Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015415:Biomarkers; D000067397:Nerve Agents; D009943:Organophosphorus Compounds; D002091:Butyrylcholinesterase
keywords: Butyrylcholinesterase; aging; hydrolysis; organophosphorus nerve agents; quantitative mass spectrometry