title: A robust high-throughput sample preparation and liquid chromatography/tandem mass spectrometry method for the quantitation of β-lyase metabolites of sulfur mustard as 1,1'-sulfonylbis-[2-(methylthio)ethane] in human urine.
abstract: BACKGROUND
  Sulfur mustard (HD) is a major chemical warfare agent threat to humans. Since World War I, several incidents of human exposure to sulfur mustard have been reported. In order to assist health professionals during an exposure event and support biological monitoring, a rapid analytical method is required to measure the exposure of humans to HD.
  
  
  METHODS
  The β-lyase metabolites of HD, 1-methylsulfinyl-2-[2-(methylthio)ethylsulfonyl]ethane (MSMTESE) and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) were reduced to the single biomarker, 1,1'-sulfonylbis-[2-(methylthio)ethane] (SBMTE), using titanium(III) chloride. High-throughput sample preparation was performed on a Tecan Freedom EVO liquid handler and analysis was performed by electrospray ionization liquid chromatography and tandem mass spectrometry (LC/MS/MS) in the multiple-reaction monitoring mode.
  
  
  RESULTS
  Each analytical run consisted of a matrix blank, calibration standards (0.1-100 ng/mL), low quality controls (QCs), 2.5 ng/mL, and high QCs, 25.0 ng/mL, of SBMTE in human urine. The method was validated with 20 analytical runs performed by four analysts. The mean calculated concentrations of the low and high QCs were 2.52 and 25.5 ng/mL with relative standard deviations of 3.6% and 2.3%, respectively.
  
  
  CONCLUSIONS
  This semi-automated method has few manual transfer steps, thus minimizing common manual errors and saving time. Therefore, this method would be very helpful to responding laboratories in a large-scale exposure event related to HD.
authors.affiliation: Division of Consolidated Laboratory Services, Commonwealth of Virginia, Richmond, VA 23219, USA. kesava.muntha@dgs.virginia.gov
authors.forename: Muntha K
authors.initials: MK
authors.lastname: Reddy
authors.forename: Christopher
authors.initials: C
authors.lastname: Nixon
authors.forename: Shane A
authors.initials: SA
authors.lastname: Wyatt
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Croley
mesh_terms: D015415:Biomarkers / Q000652:urine*; D002619:Chemical Warfare Agents; D002853:Chromatography, Liquid / Q000379:methods*; D004781:Environmental Exposure / Q000032:analysis; D006801:Humans; D008190:Lyases / Q000378:metabolism; D009151:Mustard Gas / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013440:Sulfides / Q000737:chemistry / Q000652:urine*; D013450:Sulfones / Q000737:chemistry / Q000652:urine*; D013454:Sulfoxides / Q000737:chemistry / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C583908:1,1'-sulfonylbis(2-(methylthio)ethane); D015415:Biomarkers; D002619:Chemical Warfare Agents; D013440:Sulfides; D013450:Sulfones; D013454:Sulfoxides; C073452:1,1'-sulfonylbis(2-(methylsulfinyl)ethane); C073451:1-methylsulfinyl-2-(2-(methylthio)ethylsulfonyl)ethane; D008190:Lyases; D009151:Mustard Gas