title: Lewisite Metabolites in Urine by Solid Phase Extraction-Dual Column Reversed-Phase Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry.
abstract: Lewisite (2-chlorovinyldichloroarsine) is a chemical warfare agent developed during World War I. A quantitative method using solid phase extraction (SPE) followed by dual column liquid chromatography (LC)-isotope dilution tandem mass spectrometry (MS-MS) was developed for the determination of (2-chlorovinyl)arsonic acid (CVAOA), a metabolite of Lewisite, in human urine. The sample was treated with hydrogen peroxide to oxidize any (2-chlorovinyl)arsonous acid (CVAA) that remained in the trivalent arsenic oxidation state. There was 1.19% (arsenic purity) of bis-(2-chlorovinyl)arsinic acid (BCVAOA), a minor Lewisite metabolite, in the stock CVAA material. The high-throughput method qualitatively assessed BCVAOA simultaneously utilizing normal-phase silica SPE followed by reversed-phase C18 LC for an orthogonal separation. The chromatographic method results in a 5.8-min cycle time with adequate retention (k' = 2.4) of CVAOA. The mass spectrometer was operated in positive electrospray ionization mode with quantitative m/z 186.9→61.0 and confirmation 186.9→91.0 mass transitions. This selective method demonstrated linearity, accuracy and reproducibility for the clinically relevant calibration range (25-3,200 µg/L as CVAA). The method detection limit was 3.3 µg/L as CVAA from a 10 µL injection. This LC-MS-MS emergency response method has a throughput of >240 samples (2.5 extracted 96-well plates) per day.
authors.affiliation: Florida Department of Health, Bureau of Public Health Laboratories, 1217 N. Pearl St, Jacksonville, FL 32202, USA alcic@flhealth.gov.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Palcic
authors.affiliation: NMS Labs, 3701 Welsh Rd, Willow Grove, PA 19090, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Donovan
authors.affiliation: Florida Department of Health, Bureau of Public Health Laboratories, 1217 N. Pearl St, Jacksonville, FL 32202, USA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Jones
authors.affiliation: Florida Department of Health, Bureau of Public Health Laboratories, 1217 N. Pearl St, Jacksonville, FL 32202, USA.
authors.forename: E Lindsay
authors.initials: EL
authors.lastname: Flagg
authors.affiliation: Florida Department of Health, Bureau of Public Health Laboratories, 1217 N. Pearl St, Jacksonville, FL 32202, USA.
authors.forename: Redentor A
authors.initials: RA
authors.lastname: Salonga
authors.affiliation: Florida Department of Health, Bureau of Public Health Laboratories, 1217 N. Pearl St, Jacksonville, FL 32202, USA.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Mock
authors.affiliation: Florida Department of Health, Bureau of Public Health Laboratories, 1217 N. Pearl St, Jacksonville, FL 32202, USA.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Asirvatham
mesh_terms: D001152:Arsenicals / Q000032:analysis / Q000652:urine*; D002619:Chemical Warfare Agents / Q000032:analysis / Q000378:metabolism*; D002853:Chromatography, Liquid; D006801:Humans; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry
chemical_list: D001152:Arsenicals; D002619:Chemical Warfare Agents; C035965:lewisite