Stabilization and gas chromatographic analysis of the four stereoisomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) in rat blood

Benschop, H. P.; Bijleveld, E. C.; Otto, M. F.; Degenhardt, Carla E. A. M.; Helden, H.P.M. van; Jong, L.P.A. de

doi:10.1016/0003-2697(85)90172-1

Cited by 48 publications

(14 citation statements)

References 22 publications

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“…The method for the construction and a representative example of a set of calibration curves for the four stereoisomers of soman have been published (Benschop et al 1985(Benschop et al , 1987.…”

Section: Methodsmentioning

confidence: 99%

“…The nitrogen content in the polymer was 3.35%. Further materials were as described before (Benschop et al 1985(Benschop et al , 1987.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples for gas chromatographic analysis of soman isomers were stabilized and worked up as described before (Benschop et al 1985(Benschop et al , 1987. Gas chromatography was performed on a Carlo Erba HRGC 5360, equipped with a TCT injector, a MUSIC system (Chrompack) for two-dimensional chromatography, and an NP detector.…”

Section: Methodsmentioning

confidence: 99%

“…Animal experiments for measurements of blood levels of soman isomers were performed as described earlier (Benschop et al 1985(Benschop et al , 1987. Rats weighed between 175 and 205 g and guinea pigs between 538 and 1000 g. The LDs0 values of C( +)P( ___)-soman (i.v.)…”

Section: Methodsmentioning

confidence: 99%

“…CBDP was synthesized in house (Eto et al 1962) and had a purity of 98% according to GLC and NMR analyses. L-Chirasil Val was also synthesized in house, as described before (Benschop et al 1985). The nitrogen content in the polymer was 3.35%.…”

Section: Methodsmentioning

confidence: 99%

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Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in rats and guinea pigs

Due¹,

Trap²,

Wiel

et al. 1993

Arch Toxicol

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Pretreatment of rats and guinea pigs with the specific carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) reduces the LD50 of the nerve agent C(+/-)P(+/-)-soman in these species to the same range as in primates. This suggests that such CBDP-pretreated animals can be used in investigations that are relevant for prophylaxis and therapy of intoxication with C(+/-)P(+/-)-soman in primates including humans. In order to test this hypothesis we have studied the toxicokinetics of the toxic C(+/-)P(-)-isomers of soman in artificially respirated and CBDP-pretreated rats and guinea pigs at intravenous doses corresponding to 6x LD50. A comparison of the areas under the curve (AUCs) of the blood levels of C(+/-)P(-)-soman in pretreated and non-pretreated animals at the same absolute dose shows extreme nonlinearity with dose, indicating that CBDP occupies highly reactive binding sites which are no longer available for sequestration of the soman isomers. The AUCs of C(+/-)P(-)-soman at equitoxic doses of 6x LD50 are reduced by pretreatment with CBDP from 1683 to 464 ng.min.ml-1 in rats and from 978 to 176 ng.min.ml-1 in guinea pigs, which is in the range of the AUC in non-pretreated marmosets at an equitoxic dose (419 ng.min.ml-1). The blood levels of the C(+/-)P(-)-isomers in marmosets and CBDP rats are rather similar during the first 7 min, but persist in CBDP rats for 2 h longer at toxicologically relevant levels than in marmosets.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Methodsmentioning

confidence: 99%

“…The nitrogen content in the polymer was 3.35%. Further materials were as described before (Benschop et al 1985(Benschop et al , 1987.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in rats and guinea pigs

Due¹,

Trap²,

Wiel

et al. 1993

Arch Toxicol

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The Chemistry of Organophosphorus Chemical Warfare Agents

Black

Harrison

2009

Patai's Chemistry of Functional Groups

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Introduction Historical Development Synthesis Chemical and Physical Properties Decontamination Spectroscopic Analysis Chromatographic Analysis Trace Analysis of Nerve Agents and their Degradation Products in Verification Generic Detection of Nerve Agents Mechanism of Action Toxicodynamics Therapy and Pretreatment Structure—Toxicity Relationships Control Under the Chemical Weapons Convention

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Chiral Separation of G‐type Chemical Warfare Nerve Agents via Analytical Supercritical Fluid Chromatography

Kasten¹,

Zulli

Jones

et al. 2014

Chirality

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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. Chirality 26:817–824, 2014. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc.

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Stabilization and gas chromatographic analysis of the four stereoisomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) in rat blood

Cited by 48 publications

References 22 publications

Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in rats and guinea pigs

Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in rats and guinea pigs

The Chemistry of Organophosphorus Chemical Warfare Agents

Chiral Separation of G‐type Chemical Warfare Nerve Agents via Analytical Supercritical Fluid Chromatography

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