Detection of metabolites of toxic alkylmethylphosphonates in biological samples

Abstract

The major metabolites and breakdown products of some toxic organophosphonates are their respective alkymethylphosphonic acids. These acids ionize at physiological pH and are not amenable to gas chromatographic analysis in their underivatized forms. Their detection in biological samples has been difficult because of their presence at only trace levels. Existing analytical methods were developed mainly for measuring these phosphonic acids in environmental samples and at higher concentrations. In this study, we devised a gas chromatographic/mass spectrometric method to provide confirmation and quantification of the organophosphonic acids of soman (GD), sarin (GB) and GF in blood and urine. This report describes the various derivatization conditions that we have studied and demonstrates the characteristic mass spectra by different ionization techniques.

Laboratory Identification of the Nerve Gas Hydrolysis Products Alkyl Methylphosphonic Acids and Methylphosphonic Acid, by Gas Chromatography-mass Spectrometry after <i>tert</i>-Butyldimethylsilylation

“…21) Several derivatization techniques for nerve gas hydrolysis products have been reported: trimethylsilylation, 22) methylation, 23) TBDMS 24) and pentafluorobenzylation. 25,26) TBDMS derivatives are comparatively stable and easily prepared, and have good GC peak resolution, 24) and Tsunoda 27) also applied the TBDMS derivatization procedure of the herbicides glyphosate, glufosinate and bialaphos and their metabolites by GC-MS and GC using flame ionization detection. We adopted the TBDMS derivatization technique of nerve gas hydrolysis products to GC-MS (Fig.…”

“…Moreover, some neutral compounds, such as carbohydrates, which contain hydroxide groups competed against the phosphonates in the silylation reaction and suppressed the TBDMS derivatization. 28,31) Several investigations on cleanup of nerve gas hydrolysis products using solid phase extraction (SPE) have been reported, 23,25,[32][33][34] and some drawbacks were found such as low recoveries of RMPAs and MPA and insufficient information about SPE procedures. We attempted some types of SPE including strong cation-exchanger, 28) anionexchanger and reversed-phase 31,35) followed by TBDMS derivatization.…”

Réponses analytiques aux syndromes cholinergiques et anticholinergiques

“…Les premières font appel à la CG/SM en mode sélection d'ions ou couplée à la haute résolution pour les dosages sanguins (7,8). Les secondes consistent à doser les acides alkyméthylphos-phoniques après dérivation puis CG/MS en mode courant ionique total ou en mode sélection d'ions et peuvent être appliquées au sang, aux urines, à la salive, voire à des organes (9,10,11). Dans ce second groupe, l'utilisation de l'ionisation chimique négative couplée à la spectrométrie de masse (CG/SM/ICN) permet d'abaisser considérablement la limite de détection : 60 pg/ml contre 5 ng/ml en mode sélection d'ions et 50 ng/ml en mode courant ionique total (10).…”

Pathways for the oxidation of sarin in urban atmospheres

“…Sarin hydrolysis reactions are relatively wellknown ( Figure 5). They occur within the tissues of poisoned organisms (Shih et al, 1991) and are critical to basic military decontamination procedures (Yang et al, 1992;Yoza et al, 1997). It is often the hydrolysis products which are detected to provide evidence of sarin application (Veqweij and Boter, 1975;Verweij et al, 1979 Dagostino andProvost, 1992).…”