Timur Baygildiev

Hydrophilic interaction liquid chromatography − tandem mass spectrometry methylphosponic and alkyl methylphosphonic acids determination in environmental samples after pre-column derivatization with p-bromophenacyl bromide

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.

Dilute-and-shoot rapid-separation liquid chromatography tandem mass spectrometry method for fast detection of thiodiglycolic acid in urine

A new sensitive rapid-separation liquid chromatography tandem mass spectrometry approach for the determination of thiodiglycolic acid (TDGA) in urine has been developed. The use of the “dilute-and-shoot” method helps to shorten the sample preparation stage and provides a sensitive and direct approach for TDGA determination in urine. Chromatographic separation of the analyte and other urine compounds was achieved using a reverse-phase liquid chromatography column with mobile phases consisting of 0.1% formic acid in water and acetonitrile in a gradient elution mode. For the identification and quantification of TDGA electrospray ionization-tandem mass spectrometry monitoring, two precursor-to-product ion transitions were used. The method demonstrates good linearity and has a detection limit of 50 ng mL−1 in urine.

Rapid IC–MS/MS determination of methylphosphonic acid in urine of rats exposed to organophosphorus nerve agents

A direct approach for the determination of a specific hydrolysis product of organophosphorus nerve agents such as methylphosphonic acid (MPA) in urine by ion chromatography and tandem mass spectrometry (IC-MS/MS) has been developed. The first advantage of the proposed approach is a rapid and simple sample preparation, which does not require a large sample volume, complicated and laborious preconcentration and derivatization steps, and takes less than 7min per sample. The second advantage is the fast and selective IC determination of MPA carried out on a noncommercial anion exchanger based on a poly(styrene-co-divinylbenzene) (PS-DVB) substrate with a high degree of crosslinking and a covalently-bonded branched functional layer, which enables complete resolution of MPA from major urine matrix components and allows one to overcome matrix effects. Hyphenation of IC with tandem mass spectrometry results in highly sensitive and reliable MPA determination with the lowest detection limit (4ngmL-1) reported so far for HPLC determination of MPA in urine. The proposed approach is successfully applied for the analysis of urine from rats exposed to nonlethal doses of organophosphorus nerve agents such as sarin, soman, and VR in up to 13days after initial exposure, which shows the possibility to verify the nerve agent exposure after a long period of time.

A validated LC–MS/MS method for fast detection of thiodiglycolic acid in aqueous samples

ABSTRACT A novel sensitive screening method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) has shown the feasibility of separation and detection of thiodiglycolic acid in aqueous samples. The analysis of this compound is of interest since it is specific microbiological metabolite of thiodiglycol, which is precursor and degradation product of chemical warfare agent sulfur mustard. The LC–electrospray ionisation (ESI)–MS method provides a sensitive and direct approach for thiodiglycolic acid identification and quantification using non-extracted non-derivitised samples from aqueous solutions. Chromatographic separation of the thiodiglycolic acid was produced using a reverse phase LC column with gradient mobile phases consisting of 0.1% formic acid in water and acetonitrile. Identification and quantification of species were achieved using ESI–tandem MS monitoring two precursor-to-product ion transitions for thiodiglycolic acid. The method demonstrates linearity over at least two orders of magnitude and detection limit of 10 ng...mL–1 in environmental water samples.

Determination of the hydrolysis products of nerve agents in natural waters by liquid chromatography–mass spectrometry

An approach to the determination of markers of the application of four nerve agents, S-(2-diethylaminoethyl)methylphosphonothioate, S-(2-diisopropylaminoethyl)methylphosphonothioate, bis(2N,N-diethylaminoethyl)disulfide, and bis(2-N,N-diisopropylaminoethyl)disulfide, in aqueous environmental samples by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC–MS2) is developed. The conditions of the mass spectrometric detection (selection of optimal pairs of ionic reactions) are optimized, and the program for the gradient elution in HPLC separation is adjusted. The proposed approach was tested in the analysis of real water bodies using the standard addition method. Good accuracy, reproducibility, and selectivity of determination were shown. It was demonstrated that the matrix components in the water samples have no interfering effect. Using the proposed approach, the detection limits of S-(2-diethylaminoethyl)methylphosphonothioate, S-(2-diisopropylaminoethyl)methylphosphonothioate, bis(2-N,N-diethylaminoethyl)disulfide, and bis(2-N,N-diisopropylaminoethyl)disulfide in water bodies, determined by HPLC–MS2, were found to be 0.0003, 0.003, 0.3, and 0.05 µg mL–1, respectively.

Unified strategy for HPLC-MS evaluation of bioactive compounds for quality control of herbal products

Evaluation of safety, quality and composition of herbal products and food supplements based on botanical ingredients is a matter of serious concern. For screening of botanicals in herbal products multitargeted and group-targeted approaches may be applied. In the group-targeted approach botanicals are characterized by means of an appropriate group of structurally related biomarkers compared with the multitargeted approach where a number of selected analytes are monitored based on a multiple reaction monitoring survey. In this study a unified strategy for quality control of herbal products was developed on the basis of fast ultrasound-assisted extraction, chromatographic separation and mass spectrometric quantification of bioactive compounds. A large list of unique biomarkers were monitored under almost identical chromatographic conditions, while an efficient strategy for HPLC-MS group-targeted analysis was also developed for comprehensive evaluation of chemical composition of botanicals intensively used for herbal product manufacturing. In the latter case, structurally close compounds were determined in a single ion monitoring mode for the characteristic group of fragment ions, allowing fast profiling and quality assessment of the plant material or complex food supplement. The sensitivity of the developed approaches was on the level of 1-50 ng/mL, which is higher than that of existing HPLC-UV quality control methods.

Novel analytical approaches to determination of chemical warfare agents and related compounds for verification of nonproliferation of chemical weapons

Abstract In this paper a summary of the author’s approaches for investigation of the mass spectral behavior of some chemical warfare agents (CWAs), their degradation products and metabolites, as well as the results of development of analytical methods for confirmation of nerve and blister agents application are presented. Hydrolysis and oxidation metabolites of nerve agents, sulfur mustard and lewisite were used as biomarkers of the exposure. Sensitive analytical methods have been developed for their detection, based mainly on tandem mass spectrometry coupled with liquid chromatography. Several techniques for fast screening of CWAs degradation products based on capillary electrophoresis were also proposed. Some of developed approaches were successfully applied in the frame of the proficiency testing system of the Organization for the Prohibition of Chemical Weapons.

Determination of Methylphosphonic Acid in Human Blood Plasma by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

Using high-performance liquid chromatography combined with tandem mass spectrometric detection, an approach has been developed for the determination of the most stable nerve agent biomarker, methylphosphonic acid, in human blood plasma. The proposed method is based on the derivatization of methylphosphonic acid with p-bromophenacyl bromide. The optimization of conditions for human plasma sample preparation, mass spectrometric detection conditions, and gradient elution program has been performed. The proposed approach has demonstrated satisfactory reproducibility and selectivity of the determination; the limit of detection for methylphosphonic acid in human plasma was 3 ng mL–1.

Time-Efficient LC/MS/MS Determination of Low Concentrations of Methylphosphonic Acid

A time-efficient protocol for quantification of methylphosphonic acid (MPA), a final hydrolysis product of nerve agents in aqueous environments, via liquid chromatography mass spectrometry is described. Chromatographic separation and mass spectrometry detection conditions are optimized to enable high sensitivity, selectivity, and accuracy of the approach and to eliminate impeding matrix effects associated with the analysis of water samples of natural origin. The developed technique is tested by analyzing the samples of natural waters that are spiked with a known quantity of MPA. With direct LC/MS/MS, the detection limit for MPA in natural waters is 10 ng/mL.

Determination of 2-chlorovinylarsonous acid and 2-chlorovinylarsonic acid in water by capillary electrophoresis with direct spectrophotometric detection

An approach for determining 2-chlorovinylarsonous acid and 2-chlorovinylarsonic acid (decomposition products of such blister agent as lewisite) in water by capillary zone electrophoresis was proposed. The conditions of determination such as the wavelength and mode of detection, the composition of running buffer solution, the injection volume, and the program for conditioning the capillary were optimized. The developed method is characterized by high accuracy, reproducibility, selectivity, and the absence of interfering effects of the matrix of natural water. The method was used to analyze various water samples, and the accuracy was confirmed by the “added-found” technique. The limits of detection of 2-chlorovinylarsonous acid and 2-chlorovinylarsonic acid in water samples were determined by direct spectrophotometric detection at λ = 195 nm to be 0.3 and 0.5 mg L–1, respectively.