Validation and application of a GC-MS method for determining soman concentration in rat plasma following low-level vapor exposure.

A method for determining the chemical warfare agent soman (GD) in rat plasma has been validated and applied to low-level inhalation exposure studies currently being conducted. This method utilizes a fluoride ion-based regeneration assay with isotope dilution followed by large volume injection gas chromatography with ammonia chemical ionization mass spectrometric detection. Following sample preparation by solid phase extraction, chromatographic separation was achieved using a 14% cyanopropylphenyl/86% dimethyl polysiloxane capillary column with a total run time of 18.

Quantification of nerve agent VX-butyrylcholinesterase adduct biomarker from an accidental exposure.

The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure.

A rapid and sensitive technique for assessing exposure to VX via GC-MS-MS analysis.

A rapid and sensitive method for the determination of the chemical warfare agent VX in plasma taken from Göttingen minipigs has been developed using isotope-dilution gas chromatography-tandem mass spectrometry (GC-MS-MS). Chromatographic separation was achieved on a 5% diphenyl/95% dimethyl polysiloxane capillary column with a total run time of about 11 min. The analyte was detected using ammonia chemical ionization in the multiple reaction monitoring mode, following a simple extraction with 10% 2-propanol in hexane.

Kinetics of sarin (GB) following a single sublethal inhalation exposure in the guinea pig.

To improve toxicity estimates from sublethal exposures to chemical warfare nerve agents (CWNA), it is necessary to generate mathematical models of the absorption, distribution, and elimination of nerve agents. However, current models are based on representative data sets generated with different routes of exposure and in different species and are designed to interpolate between limited laboratory data sets to predict a wide range of possible human exposure scenarios. This study was performed to integrate CWNA sublethal toxicity data in male Duncan Hartley guinea pigs.

Comparison of low-level sarin and cyclosarin vapor exposure on pupil size of the Gottingen minipig: effects of exposure concentration and duration.

The current studies estimated effective (miosis) concentrations of the nerve agents' sarin (GB) and cyclosarin (GF) as a function of exposure duration in the Gottingen minipig and determined dependency of the median effective dosage (ECT50) over time. Male and female Gottingen minipigs were exposed to various concentrations of vapor GB or GF for 10, 60, or 180 min. Infrared images of the pig's pupil before, during, and after nerve agent exposure were captured digitally and pupil area was quantified.

Tolerance to the miotic effect of sarin vapor in rats after multiple low-level exposures.

Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin (GB) results in the accumulation of acetylcholine and excessive cholinergic stimulation. There are few data in the literature regarding the effects of multiple low-level exposures to GB and other organophosphorous compounds via relevant routes of exposure. Therefore, the present study was undertaken, and is the first, to investigate the effect of low-level repeated whole-body inhalation exposures to GB vapor on pupil size and cholinesterase activity in the eyes and blood.

Miotic tolerance to sarin vapor exposure: role of the sympathetic and parasympathetic nervous systems.

O-isopropyl methylphosphonofluoridate, also known as sarin or GB, is a highly toxic organophosphorous compound that exerts its effect by inhibiting the enzyme acetylcholinesterase. While the effects of a single exposure to GB vapor are well characterized, the effects of multiple exposures to GB vapor are less clear. Previous studies in the rat and guinea pig have demonstrated that multiple exposures result in tolerance to the miotic effect of nerve agents.