title: Chiral separation of G-type chemical warfare nerve agents via analytical supercritical fluid chromatography.
abstract: Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G-type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical-scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(-) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(-) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents.
authors.affiliation: Physiology and Immunology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, APG, MD.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Kasten
authors.forename: Steven
authors.initials: S
authors.lastname: Zulli
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Jones
authors.forename: Thomas
authors.initials: T
authors.lastname: Dephillipo
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Cerasoli
mesh_terms: D002619:Chemical Warfare Agents / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D013058:Mass Spectrometry; D010755:Organophosphates / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D009943:Organophosphorus Compounds / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D012524:Sarin / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D012999:Soman / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism
chemical_list: D002619:Chemical Warfare Agents; D010755:Organophosphates; D009943:Organophosphorus Compounds; D012999:Soman; D012524:Sarin; C009374:tabun; C053914:cyclohexyl methylphosphonofluoridate
keywords: Regis WhelkO1; chiral stationary phase (CSP); cyclosarin (GF); organophosphorus (OP); sarin (GB); soman (GD); tabun (GA)