ethyl-methylphosphonic-acid and pinacolyl-methylphosphonic-acid

Once exposed to the environment organophosphate nerve agents readily degrade by rapid hydrolysis to the corresponding alkyl methylphosphonic acids which do not exist in nature. These alkyl methylphosphonic acids are finally slowly hydrolyzed to methylphosphonic acid. Methylphosphonic acid is the most stable hydrolysis product of organophosphate nerve agents, persisting in environment for a long time. A highly sensitive method of methylphosphonic acid and alkyl methylphosphonic acids detection in dust and ground mixed samples has been developed and validated. The fact that alkyl methylphosphonic acids unlike methylphosphonic acid did not react with p-bromophenacyl bromide under chosen conditions was discovered. This allowed simultaneous chromatographic separation and mass spectrometric detection of derivatized methylphosphonic acid and underivatized alkyl methylphosphonic acids using HILIC-MS/MS method. Very simple sample pretreatment with high recoveries for each analyte was developed. Methylphosphonic acid pre-column derivate and alkyl methylphosphonic acids were detected using tandem mass spectrometry with electrospray ionization after hydrophilic interaction liquid chromatography separation. The developed approach allows achieving ultra-low detection limits: 200 pg mL(-1) for methylphosphonic acid, 70 pg mL(-1) for ethyl methylphosphonic acid, 8 pg mL(-1) for i-propyl methylphosphonic acid, 8 pg mL(-1) for i-butyl methylphosphonic acid, 5 pg mL(-1) for pinacolyl methylphosphonic acid in the extracts of dust and ground mixed samples. This approach was successfully applied to the dust and ground mixed samples from decommissioned plant for the production of chemical weapons.

Topics: Acetophenones; Chromatography, Liquid; Environmental Monitoring; Hydrolysis; Hydrophobic and Hydrophilic Interactions; Organophosphonates; Organophosphorus Compounds; Soman; Tandem Mass Spectrometry; Water Pollutants, Chemical

A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.

Topics: Biotransformation; Chemical Warfare Agents; Fluorobenzenes; Gas Chromatography-Mass Spectrometry; Humans; In Vitro Techniques; Indicator Dilution Techniques; Limit of Detection; Liquid-Liquid Extraction; Organophosphonates; Organophosphorus Compounds; Organothiophosphorus Compounds; Sarin; Soman

Three primary nerve agent degradation products (ethyl-, isopropyl- and pinacolyl methylphosphonic acid) have been determined in water samples using on-line solid phase extraction-liquid chromatography and mass spectrometry (SPE-LC-MS) with electrospray ionisation. Porous graphitic carbon was employed for analyte enrichment followed by hydrophilic interaction chromatography. Diethylphosphate was applied as internal standard for quantitative determination of the alkyl methylphosphonic acids (AMPAs). By treating the samples with strong cation-exhange columns on Ba, Ag and H form, the major inorganic anions in water were removed by precipitation prior to the SPE-LC-MS determination. The AMPAs could be determined in tap water with limits of detection of 0.01-0.07 μg L(-1) with the [M-H](-) ions extracted at an accuracy of ±5 mDa. The within and between assay precisions at analyte concentrations of 5 μg L(-1) were 2-3%, and 5-9% relative standard deviation, respectively. The developed method was employed for determination of the AMPAs in three natural waters and a simulated waste water sample, spiked at 5 μg L(-1). Recoveries of ethyl-, isopropyl- and pinacolyl methylphosphonic acid were 80-91%, 92-103% and 99-106%, respectively, proving the applicability of the technique for natural waters of various origins.

Topics: Chemical Warfare Agents; Chromatography, Liquid; Equipment Design; Fresh Water; Graphite; Limit of Detection; Mass Spectrometry; Organophosphonates; Organophosphorus Compounds; Porosity; Solid Phase Extraction; Soman; Water; Water Pollutants, Chemical

Separation and detection of seven V-type (venomous) and G-type (German) organophosphorus nerve agent degradation products by gas chromatography with inductively coupled plasma mass spectrometry (GC-ICPMS) is described. The nonvolatile alkyl phosphonic acid degradation products of interest included ethyl methylphosphonic acid (EMPA, VX acid), isopropyl methylphosphonic acid (IMPA, GB acid), ethyl hydrogen dimethylamidophosphate sodium salt (EDPA, GA acid), isobutyl hydrogen methylphosphonate (IBMPA, RVX acid), as well as pinacolyl methylphosphonic acid (PMPA), methylphosphonic acid (MPA), and cyclohexyl methylphosphonic acid (CMPA, GF acid). N-(tert-Butyldimethylsilyl)-N-methyltrifluroacetamide with 1% TBDMSCl was utilized to form the volatile TBDMS derivatives of the nerve agent degradation products for separation by GC. Exact mass confirmation of the formation of six of the TBDMS derivatives was obtained by GC-time of flight mass spectrometry (TOF-MS). The method developed here allowed for the separation and detection of all seven TBDMS derivatives as well as phosphate in less than ten minutes. Detection limits for the developed method were less than 5 pg with retention times and peak area precisions of less than 0.01 and 6%, respectively. This method was successfully applied to river water and soil matrices. To date this is the first work describing the analysis of chemical warfare agent (CWA) degradation products by GC-ICPMS.

Topics: Chemical Warfare Agents; Gas Chromatography-Mass Spectrometry; Organophosphonates; Organophosphorus Compounds; Organosilicon Compounds; Organothiophosphorus Compounds; Rivers; Sensitivity and Specificity; Soil; Soman; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Temperature; Time Factors; Volatilization; Water Pollutants, Chemical

For proof of the presence of chemical warfare agents sarin, soman and VX, a rapid, accurate and sensitive method which allows us to determine their hydrolysis products ethyl methylphosphonic acid, isopropyl methylphosphonic acid and pinacolyl methyl phosphonic acid was explored by using continuous flow frit fast atom bombardment (FAB) LC-MS and LC-MS-MS. After derivatization of analytes with p-bromophenacyl bromide, LC-MS-MS analyses for screening were performed by a flow injection method. The three alkyl methylphosphonic acids (AMPAs) were eluted within 5 min, and the detection limits for the three AMPAs ranged from 1 to 5 ng/ml. For confirmation of the screening results, LC-MS-MS analysis with chromatographic separation was conducted by using a narrow bore column. The three AMPAs were all eluted with excellent separation within 25 min, and the detection limits ranged from 1 to 20 ng/ml. Quantitative measurement was performed by LC-MS in selected ion monitoring (SIM) mode with chromatographic separation. Linear calibration curves were obtained for the three AMPAs and the detection limits ranged from 0.5 to 3 ng/ml. The relative standard deviation for peak area ranged from 3.4 to 6.0% at 50 ng/ml for the three AMPAs.

Topics: Chemical Warfare Agents; Chromatography, High Pressure Liquid; Humans; Hydrolysis; Organophosphonates; Organophosphorus Compounds; Sensitivity and Specificity; Soman; Spectrometry, Mass, Fast Atom Bombardment; Water

A method of detecting signature methylphosphonic acid (MPA) breakdown products of V and G nerve agents in environmental samples was developed using capillary ion electrophoresis with conductivity detection. The electrolyte (30 mM L-histidine, 30 mM 2-(N-morpholino)ethanesulfonic acid, 0.7 mM tetradecyltrimethylammonium hydroxide, and 0.03 weight% Triton X-100) allowed baseline separation of MPA, ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), and pinacolyl methylphosphonic acid (PMPA) in less than 10 min. Detector response was linear in the 6-60 micrograms/ml concentration range (correlation coefficient = 0.99) with a detection limit around 6 micrograms/ml. The application of this method for screening MPA, EMPA, IMPA, and PMPA in surface water, groundwater, and soil extracts is demonstrated.

Topics: Chemical Warfare Agents; Electrophoresis, Capillary; Nervous System; Organophosphonates; Organophosphorus Compounds; Soil; Soman; Water