Stabilization and gas chromatographic analysis of the four stereoisomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) in rat blood
article
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??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(-)-soman by free fluoride ions from soman-inhibited aliesterase, and (iii) addition of 2,2-dimethylpropyl methylphosphonofluoridate in order to occupy covalent binding sites for C(??)P(-)-soman. The stereoisomers of soman and internal standard are extracted from the blood-stabilizing buffer mixture with a Sep-Pak C18 cartridge and are subsequently eluted with ethyl acetate with overall extraction recoveries of 52 ?? 8%. The four soman stereoisomers are resolved and analyzed on a wide-bore capillary Chirasil Val column, synthesized, and coated in house, which also resolves the internal standard C(??)P(+)-1,2,2-[U-2H]trimethylpropyl methylphosphonofluoridate from C(??)P(??)-soman. Alternatively, the gas chromatographic analysis can be performed on a wide-bore capillary Chirasil Val column, identical with the commercially available Chirasil Val column, when combined in series with a Carbowax 20M column. This system resolves the four stereoisomers of soman and the internal standard C(-)P(+)-1,2,2-trimethylpropyl [U-2H]methylphosphonofluoridate. Using an alkali flame ionization detector, the detection limit of our procedure is ca. 250 pg soman isomer/blood sample.
Topics
G agentsStereochemistryBloodRatsStabilityGC - Gas chromatographyMetal complexesAluminumFluoridesSoman, 96-64-0Deuterium, 7782-39-0Indicators and reagentsAnimal cellBlood and hemopoietic systemMethodologyNonhumanRatStereoisomerismAnimalDrug stabilityHydrogen-Ion ConcentrationIndicators and ReagentsKinetics
TNO Identifier
109354
ISSN
0003-2697
Source
Analytical Biochemistry, 151, pp. 242-253.
Pages
242-253
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