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

@article{Benschop1985StabilizationAG,
  title={Stabilization and gas chromatographic analysis of the four stereoisomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) in rat blood.},
  author={H. Benschop and E. Bijleveld and M. Otto and C. Degenhardt and H. V. van Helden and L. D. de Jong},
  journal={Analytical biochemistry},
  year={1985},
  volume={151 2},
  pages={
          242-53
        }
}
A method for the stabilization and gas chromatographic analysis of the four stereoisomers of C(+/-)P(+/-)-1,2,2-trimethylpropyl methylphosphonofluoridate (C(+/-)P(+/-)-soman) in rat blood samples is described. Satisfactory stabilization of all four stereoisomers is obtained by (i) acidification of the blood sample to pH 4.2 at 0 degrees C, to stabilize the C(+/-)P(+) isomers, (ii) addition of aluminum ions (2.5 mM) for complexation of fluoride ions, which prevents regeneration of C(+/-)P… Expand
Assay of the chiral organophosphate, soman, in biological samples.
TLDR
Using a splitless or on-column injection technique and alkali flame ionization detection, the minimum detectable concentration is 30 pg/3-ml blood sample for the two isomers which do not have anticholinesterase activity and are rapidly degraded in rat blood due to hydrolysis by phosphorylphosphatases. Expand
Hydrolysis of the four stereoisomers of soman catalyzed by liver homogenate and plasma from rat, guinea pig and marmoset, and by human plasma.
Stereoselective hydrolysis at pH 7.5 and 37 degrees of C(+/-)P(+/-)-soman by liver homogenate and plasma from rat, guinea pig and marmoset, and by human plasma is studied by using the four singleExpand
Toxicokinetics of soman: Species variation and stereospecificity in elimination pathways
TLDR
Intraspecies nonlinearity with dose in the toxicokinetics of the C(+/-)P(-)-isomers is related to heterogeneous reactivity of the binding sites, leading to increasing "toxico-availability" in the reversed order. Expand
Stereoselective hydrolysis of soman in human plasma and serum.
TLDR
It can be concluded that a phosphorylphosphatase hydrolyzes the P(+)-isomers in a stereoselective way, the P(--isomers either not being affected by this (these) enzyme(s) or the mechanism of catalysis being fundamentally different, thus suggesting that more than one enzyme is involved in the degradation of soman. Expand
Hydrolysis and binding of a toxic stereoisomer of soman in plasma and tissue homogenates from rat, guinea pig and marmoset, and in human plasma.
TLDR
The spontaneous and enzyme-catalyzed hydrolytic activities found for degradation of C(+)P(-)-soman in organs participating in central elimination are sufficiently high to account for the terminal half-life times of the isomer found in toxicokinetic studies for the blood concentration after intoxication with 2-6 LD50. Expand
Toxicokinetics of the four stereoisomers of the nerve agent soman in atropinized rats--influence of a soman simulator.
TLDR
Both this reintoxication phenomenon due to the presence of toxicologically significant C(+/-)P(-)-soman levels up to 4 hr after intoxication and its antagonism via PDP pretreatment can be understood on the basis of the toxicokinetic measurements. Expand
Gas chromatographic separation of the stereoisomers of organophosphorus chemical warfare agents using cyclodextrin capillary columns
The synthesis of the organophosphorus nerve agents sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) produces a mixture of two stereoisomers except for soman where four stereoisomers areExpand
Bioanalysis of the enantiomers of (+/-)-sarin using automated thermal cold-trap injection combined with two-dimensional gas chromatography.
TLDR
A fully automated multidimensional gas chromatographic system with thermal desorption injection and alkali flame detection was developed for analysis of the enantiomers of the nerve agent (+/-)-sarin and stabilization of sarin in the blood sample by acidification and addition of an excess of a competitive organophosphorus compound (neopentyl sarin). Expand
Pharmacokinetics of the soman simulant 1,2,2-trimethylpropyl dimethylphosphinate (PDP) in rats
TLDR
The kinetic conditions for which soman simulants were designed, i.e., to displace soman from reversible binding sites by means of a “mass effect”, are clearly fulfilled and hitherto unidentified effects other than competition between PDP and C(±)P(−)-soman for binding sites may also contribute to the beneficial effects of PDP pretreatment in soman intoxication. Expand
Soman levels in kidney and urine following administration to rat, guinea pig, and marmoset.
TLDR
It is concluded, that this reabsorption does probably not explain the previously observed persistence and "late toxicity" of C(+/-)P (+/-)-soman in rats, although the amount of renally excreted C( +/-)Soman (ca. 1% of the administered dose) should be sufficient for a toxicologically significant effect. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 21 REFERENCES
Formation of soman (1,2,2-trimethylpropyl methylphosphonofluoridate) via fluoride-induced reactivation of soman-inhibited aliesterase in rat plasma
Abstract After incubation (37°) of rat blood or plasma with the nerve agent soman, (CH 3 ) 3 C(CH 3 )C(H)O(CH 3 )P(O)F (7.7 μM), for 10 min, only a small amount of this organophosphate (7 or 1%,Expand
Isolation, in vitro activity, and acute toxicity in mice of the four stereoisomers of soman.
TLDR
The isolation of the four stereoisomers of the nerve agent pinacolyl methylphosphonofluoridate (soman) is reported, with more than 99% optical purity, and it is suggested that mice challenged with a lethal dose of soman (sc) are killed primarily by the C(-)P(-)-isomer. Expand
Isolation, anticholinesterase properties, and acute toxicity in mice of the four stereoisomers of the nerve agent soman.
TLDR
The isolation of these stereoisomers of the nerve agent pinacolyl methylphosphonofluoridate with more than 99% optical purity is reported, indicating that small rate ratios may be overruled by other stereospecific effects, e.g., in vivo rates of detoxification. Expand
GAS CHROMATOGRAPHIC SEPARATION AND IDENTIFICATION OF THE FOUR STEREOISOMERS OF 1,2,2‐TRIMETHYLPROPYL METHYLPHOSPHONOFLUORIDATE (SOMAN). STEREOSPECIFICITY OF IN VITRO DETOXIFICATION REACTIONS
Die Trennung der vier Stereoisomeren (C(-)PI2-), C(-)P(+),(C(+)P(-), C(+)P(+)) des Nervenreagenzes Soman (I) gelingt durch opplung der zur Trennung der Epimeren verwendeten Chirasil-Val-Saule (anExpand
Role of aliesterase in organophosphate poisoning.
  • J. Clement
  • Medicine
  • Fundamental and applied toxicology : official journal of the Society of Toxicology
  • 1984
TLDR
In mice plasma aliesterase appears to be an extremely important detoxification route for soman in vivo. Expand
Quantification of the organophosphorus nerve agent soman by competitive inhibition enzyme immunoassay using monoclonal antibody
TLDR
The production of a mouse monoclonal antibody that binds to soman is discussed and the use of this antibody in a competitive inhibition enzyme immunoassay (CIEIA) capable of quantifying levels of soman as low as 1.0 x 10v6M (200ppb) is described. Expand
Synthesis and properties of a novel chiral stationary phase for the resolution of amino acid enantiomers
Abstract A novel chiral stationary phase hase been synthesized by grafting L-valinetert.-butylamide on to modified polycyanopropylmethyl phenylmethyl silicone (OV-225). This chiral phase can be usedExpand
Assay of the nerve agent Soman in serum by capillary gas chromatography with nitrogen-phosphorus detection and splitless injection
SummaryA procedure is described for the determination of the nerve agent Soman in serum. The nerve agent is separated from the serum on C18 modified silica and then eluted with benzene. TheExpand
The stability of sarin and soman in dilute aqueous solutions and the catalytic effect of acetate ion.
  • R. I. Ellin, W. Groff, A. Kaminskis
  • Chemistry, Medicine
  • Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes
  • 1981
TLDR
An enzymic method has been used to measure low levels of organophosphonates and acetate ion was found to significantly accelerate hydrolysis. Expand
Quantitation of free Soman in nervous tissue and blood. A preliminary communication.
TLDR
By means of quantitation of Soman in blood and nervous tissue, mass fragmentography and the quantitative measurements involved use of a deuterated internal standa/~d. Expand
...
1
2
3
...