A method has been developed for the determination of tetrodotoxin in water, blood plasma, and drugs at a level of 0.05—1.0 µg/mL. The method is based on the hydrolytic decomposition of tetrodotoxin by a sodium hydroxide solution, extraction of 2-amino-6-hydroxymethyl-8-hydroxyquinazoline using liquid–liquid extraction, preparation of its derivative by reaction with N,O-bis(trimethylsilyl)trifluroacetamide, and the determination of the derivative by gas–liquid chromatography with a mass-spectrometric detector.

Brominated aromatic compounds are intermediates for drug syntheses [1 – 3]. 3,4-Dimethylaminobenzene (o-xylidine), which is obtained in turn from 4-bromo-o-xylene, is an intermediate in the synthesis of vitamin B 2 [4]. Classical (direct) bromination of o-xylene (I) by liquid Br 2 in the presence of catalytic amounts of iron and iodine is well known [5, 6]. The yield of monobrominated I reaches 89 – 93%. According to the literature [7], monobromo-o-xylene is formed as a mixture of the 3and 4-bromo-o-xylene isomers in a 25:75% ratio. Direct bromination of aromatic compounds suffers from wasteful use of Br 2 , half of which is converted to HBr. This is an economic and ecological problem for large-scale operations. An additional processing unit is necessary to trap the HBr released by the reaction. Waste HBr (off-gas) should be reprocessed to recover expensive bromine. Bromination of I in the presence of H 2 O was proposed in order to avoid the HBr trapping unit [8]. Oxidative bromination is widely used to introduce Br into an aromatic ring and allows more complete utilization of expensive Br 2 . Nitric acid, H 2 O 2 , Cl 2 , and ozone were proposed as oxidants. Thus, H 2 O 2 [9, 10] and NaClO [11] were used for oxidative bromination of I. The present work examines the use of an alkali-metal bromate as the oxidant to produce monobromo-o-xylene. Alkali-metal bromates have been used to synthesize bromoarenes. However, the bromate was used in all published examples not as an oxidant but as a Br donor. Thus, sodium or potassium bromate in the presence of a large excess of H 2 SO 4 is commonly used to introduce Br into a deactivated benzene ring [12]. The reaction occurs under forcing conditions. Part of the starting arene is destroyed because of the elevated temperature and high acidity of the medium (the H 2 SO 4 content in the reaction mixture is 40%) [13]. Japanese researchers proposed the NaBrO 3 /NaHSO 3 system for bromination of alkylarenes. However, the side chain was brominated in addition to the ring. The fraction of á-bromo-o-xylene exceeded 11% for I [14]. Indian researchers used a bromide/bromate mixture in the presence of an excess of a strong mineral acid in order to introduce Br into an aromatic ring [15]. An analysis of the literature showed that a significant excess of the brominating reagents was required if the aforementioned methods were used to introduce Br into an aromatic ring. Furthermore, a significant amount of aqueous waste containing complicated mixtures of inorganic compounds was formed. We studied oxidative bromination by liquid Br 2 or HBr in the presence of an alkali-metal bromate as the oxidant using monobromo-o-xylene as an example. Pharmaceutical Chemistry Journal, Vol. 50, No. 3, June, 2016 (Russian Original Vol. 50, No. 3, March, 2016)

Oxidative bromination of o -xylene with liquid bromine or hydrobromic acid in aqueous solution in the presence of an alkali-metal bromate as the oxidizing agent was studied. The proposed method allowed the amount of wastes to be reduced while maintaining a high yield of bromo- o -xylene, which is used in the synthesis of vitamin B 2 .

Изучено окислительное бромирование o-ксилола жидким бромом или бромистоводородной кислотой в водной среде в присутствии бромата щелочного металла, используемого в качестве окислителя. Предлагаемый метод позволяет сократить количество отходов при сохранении высокого выхода бром-o-ксилола, применяемого в синтезе витамина В2.

Разработана методика определения 2-эндо-(6-хлорпиридин-3-ил)-7-азабицикло-[2.2.1]гептана (эпибатидин) и 2-эндо-(6-хлорпиридин-3-ил)-7-азабицикло[2.2.1]гептан-7-ола (биомаркер эпибатидина) в плазме крови на уровне 1 ? 10-5 1 ? 10-3 мг/мл. Методика основана на извлечении компонентов из плазмы крови жидкостно-жидкостной экстракцией и газохроматографическом определении с использованием термоионного или масс-спектрального детекторов. С целью снижения предела обнаружения эпибатидина и его биомаркера при использовании масс-спектрометрического детектора в методику включена стадия дериватизации с помощью N,O-бис(триметилсилил)трифторацетамида или 2,3,4,5,6-пентафторбензилбромида.

A method has been developed for the determination of 2-endo(6′-chloropyridin-3′-yl)-7-azabicyclo[2.2.1]heptane (epibatidine) and 2-endo(6′-chloropyridin-3′-yl)-7-azabicyclo[2.2.1]heptane-7-ol (epibatidine biomarker) in blood plasma at a level of 1 × 10−5–1 × 10−3 mg/mL. The method is based on the extraction of components from blood plasma by liquid-liquid extraction followed by gas-chromatographic determination using thermionic or mass spectrometric detectors. To reduce the limit of detection for epibatidine and its biomarker in using the mass-spectrometric detector, a derivatization stage using N,O-bis(trimethylsilyl)trifluoroacetamide or 2,3,4,5,6-pentafluorobenzyl bromide has been included into the procedure.

New achiral separating bifunctional reagents, dichlorides of methylphosphonic and O-ethyl-thiophophoric acids, have been used for the quantitative determination of the enantiomeric composition of α-amino acids (alanine, valine, proline), secondary alcohols (2-octanol, 2-pentanol, 1-methoxy-2-propanol) and α-phenylethylamine. The determination of the enantiomeric composition of optically active α-amino acids, secondary alcohols, and amines is based on the transformation of compounds into symmetric diastereometers using organophosphorous achiral bifunctional reagents followed by the determination of the derivatives by gas chromatography with a mass spectral detector.

Разработана методика определения тиодигликоля, 1,1-сульфонил-бис[2-(метилсульфонил)-этна], 1-метилсульфонил-2-[2-(метилтио)этилсульфонил]этана (биомаркеры иприта), метилфосфоновой кислоты, О-этилметилфосфоновой кислоты, О-изопропилметилфосфоновой кислоты, О-пинаколилметилфосфоновой кислоты (биомаркеры фосфорорганических отравляющих веществ) в моче. Методика включает извлечение компонентов жидкостной экстракцией, получение производных, разделение газожидкостной хроматографией и детектирование пламенно-фотометрическим и масс-спектрометрическим детекторами. Методика применена для анализа образцов искусственной мочи методом “введено-найдено”.

A procedure has been developed for the determination of thioglycol, 1,1′-sulfonyl-bis[2-(methylsulfonyl)-ethane], 1-methylsulfonyl-2-[2-(methylthio)ethylsulfonyl]ethane (biomarkers of mustard agent) and methylphosphonic acid, O-ethylmethylphosphonic acid, O-isopropylmethylphosphonic acid, and O-pinacolyl methylphosphonic acid (biomarkers of organophosphoric toxic agents) in urine. The procedure includes the recovery of components by liquid extraction, derivatization, separation by gas-liquid chromatography, and detection by flame-photometric and mass spectral detectors. The procedure has been applied to the analysis of samples of artificial urine by the standard addition method.

A procedure was developed for determining traces of O -isopropyl methylphosphonofluoridate (sarin) in soils at a level of 2 × 10 −4 mg/kg. The procedure is based on solvent extraction with a hexane-benzene mixture, the preconcentration of the extract to a small volume, the synthesis of dialkyl esters using secondary alcohol aluminates, and gas-chromatographic separation on an HP-1 column with a flame ionization detector. The determination error does not exceed 29%; the time of analysis is 1 h.

Разработана методика определения микроколичеств O-изопропилового эфира фторангидрида метилфосфоновой кислоты (зарина) в почвах на уровне 2 ? 10-4 мг/кг, основанная на извлечении жидкостной экстракцией смесью растворителей гексан–бензол, концентрировании экстракта, до небольшого объема, получении диалкиловых эфиров с помощью алюминатов вторичных спиртов, разделении методом газовой хроматографии с пламенно-фотометрическим детектором на колонке НР-1. Погрешность определения не превышает 29%, продолжительность анализа составляет 1 ч.

A procedure was proposed for the gas-chromatographic determination of trace O-isobutyl-S-2-(N,N-diethylamino)ethyl ester of methylthiophosphonic acid (mixed ester, ME) in burning products formed after the detoxication of elements in building constructions, personal protection equipment, waste degassing solutions, and other production wastes (slime) at a level of (1.0–10.0) × 10−8 mg/g. The procedure is based on the extraction of ME from an analyzed material with a mixture of aqueous solutions of monoethanolamine and NaOH, its back extraction to hexane, the evaporation of the hexane layer (with the addition of HCl) to dryness, the transformation of ME into methyl ester of O-isobutylmethylphosphonic acid with the use of methanol in the presence of AgNO3, and the chromatography of the derivative on an open tubular column with the chemically modified HP-INN OWax stationary phase with the use of a flame-photometric detector.

A procedure was developed for the gas-chromatographic determination of sarin and soman in the atmospheric air of work zones and inhabited areas at a level of the maximum permissible concentration 2 × 10−5 and 1 × 10−5 mg/m3 and the tentative safe exposure level 2 × 10−7 and 1 × 10−7 mg/m3, respectively. The procedure is based on the recovery of sarin and soman from analyzed air using an absorbing solution, the extraction of sarin and soman from this solution with ethyl acetate and hexane, respectively, the evaporation of the corresponding extracts to a residual volume of 0.1 cm3, and their subsequent chromatography with flame-photometric and thermoionic detectors. The relative error in the determination of sarin and soman is 20 and 18 rel %, respectively, in the air of work zones and 27 and 23 rel %, respectively, in the air of inhabited areas.

A technique for determining the enantiomeric composition of 2-octanol and α-phenylethylamine with the use of gas chromatography on optically inactive stationary phases is proposed. The technique is based on the formation of symmetrical diastereomeric derivatives upon the interaction of enantiomers with bifunctional achiral reagents: dimethyldichlorosilane, bromochloromethane, and dibromoethane. The reagents were chosen from the viewpoint of the synthesis of diastereomers with a minimum distance between the chiral centers. This minimum distance is responsible for a difference in the energies of interaction of the derivatives with the stationary liquid phase, which is sufficient for the separation of these derivatives.

A gas-chromatographic procedure is proposed for the determination of O-isobutyl S-2-(N,N-diethylamino)ethyl methyl phosphonothioate (mixed ester) at the maximum permissible level for the working area air (5 × 10–6 mg/m3) and at the safe reference level of impact for the community air (5 × 10–8 mg/m3). The procedure is based on trapping the mixed ester from air by a chemisorbent. Next, the analyte is extracted by hexane; transformed to O-methyl-O-isobutyl methyl phosphonate by silver nitrate in methanol; and, in the case of the working area air, the methanol solution of the derivative is chromatographed. In the determination of the mixed ester in the community air, a solution of O-methyl-O-isobutyl methyl phosphonate (dialkyl methyl phosphonate) in methanol is passed through a column with an adsorbent and transferred to the chromatographic system with a thermal desorption system. The relative error of the determination of the mixed ester in the working area and community air is no more than 28 and 40 rel. %, respectively.

Procedures were developed for the determination of trace isobutyl S-2-(N,N-diethylamino)ethyl methylphosphonothioate (IBDAEMP) in soil and construction materials by gas chromatography at a level of 1 × 10–9%. The procedures are based on the extraction of IBDAEMP from test materials using an aqueous solution of monoethanolamine or chloroform saturated with ammonia, the back extraction of IBDAEMP into hexane, the evaporation of the hexane solution (with an addition of HCl) to dryness, the treatment of the residue with a solution of silver nitrate in methanol for obtaining O-isobutyl O-methyl methylphosphonate, and gas-chromatographic separation on an open tubular column with the HP–5MS chemically modified stationary phase with flame-photometric detection.

A gas chromatographic procedure is developed for the determination of β,β-dichlorodiethylsulfide (yperite, sulfur mustard) and β-chlorovinyldichloroarsine (lewisite) in the working area and community air at a level defined by the hygienic regulations for community air (2 × 10–6 and 4 × 10–6 mg/m3 for sulfur mustard and lewisite, respectively) and at the maximum permissible level for a working area (2 × 10–4 mg/m3). The procedure for the determination of sulfur mustard is based on the trapping of the analyte from air with Silochrom S-120 impregnated with Apiezon L with further extraction by a 1 : 1 acetone–hexane mixture, the evaporation of the extract to a small residual volume, and chromatography with an electron capture detector. The procedure for the determination of β-chlorovinyldichloroarsine (lewisite) involves the absorption of the analyte with a 2.2% solution of triethanolamine in 0.1 M hydrochloric acid, the conversion of lewisite to acetylene by treating the trap contents with 30% alkali solution, and the chromatography of the vapor phase using a flame ionization detector. The error of the determination is no more than ±23 rel %. The analysis takes 1.5 h.