The article describes acute problem - absence of reference standards (Federal Reference Standards) of controlled ingredients of some potent pharmaceuticals (especially narcotic and psychotropic substances) in Russia. Authors present an algorithm for solving this task. According to regulatory documents providing traceability and technical regulation in Russian Federation requires use of the Federal Reference Standards for any official quantitative studies of narcotic and psychotropic substances. Lack of the reference standards does not allow provide: legally meaningful assessment of quality of medical products; to ensure industrial safety of work with substances belonging to list of dangerous goods; to conduct quantitative forensic analysis using instrumental methods, etc. Development of the Federal Reference Standards should be organized in the framework of technological cooperation of organizations (laboratories) which has necessary licenses. Production of the highest quality standards should be organized on a specialized facility where Federal S&T Center "Inversiya" has already made Federal Reference Standards of toxic chemicals. Creation and introduction in practices Federal Reference Standards of the controlled substances will provide scientific, technical and methodological foundations in development and implementation technologies for production of potent pharmaceutical ingredients in Russian Federation and solutions in the field of criminology and chemical safety and security.

The article describes some approaches to choice of the most potent non-narcotic analgesics among agents investigated in various R&D stages. Preparations non-narcotic analgesics for relief of severe and moderate pain are relatively new area of pharmaceuticals. Their application is very important as an alternative to opiates. However, the actual number of drug candidates is very limited. As a result of the authors analysis one of the most potent non-narcotic analgesics (PNS neurons sodium channel blocker) - Tetrodotoxin (TTX) was recognized as the most promising. Currently FSUE «GosZMP» conducting preclinical studies of injectable preparation of TTX.

According to comparative analysis of medical consumption of potent analgesics in economically developed countries was justified the need to increase production of active ingredients of potent analgesics in Russia by more than ten times. Also a list of the most relevant analgesics for production for chronic patients and for use in emergency situations was provided. It was shown that the production of substances of potent analgesics in Russia by 2020 should be increased up to 5-6 tons in morphine equivalent. This amount takes into account the need to expand diversity of dosage forms suitable for patient, including transdermal, transmucosal, intranasal, and others. The proportion of natural and semi-synthetic opioid analgesics should be at least 50% of the total production in morphine equivalent. Use of genetically modified varieties of opium poppy allows to obtain the raw material with a predetermined content of target alkaloids. It is proposed to organize production of active analgesics ingredients at one of repurposed military facilities, as well as recreate biotechnological production of raw materials on the basis of genetically modified varieties of poppy. This approach allows to produce active analgesics ingredients for all pharmaceutical manufacturers of Russian Federation. It is proposed to organize production of certified reference materials of significant pharmaceutical drugs and psychotropic substances for all Russian consumers - more than 250 licensed organizations in industry, health care, law enforcement, chemical safety and security.

Application of luminescent reagents for detection of toxicants including warfare agents, pesticides and their degradation products and precursors has been systematically reviewed. Methods of organophosphorus toxicants and products of their destruction (OP) detection based on lanthanide luminescent complexes (primarily Eu3+) have the similar sensitivity as the most advanced instrumental chromatographic and biochemical assays with detection level in the range of several ppts that allows to determine supertoxicants at the safety requirements concentration levels and at appropriate analysis duration from a few seconds to 10 minutes. High selectivity of toxicants identification is achieved by means of imprinted materials, modified cyclodextrins and luminescent sensor arrays. This is the basis for development of new technologies for trace analysis of toxicants and their decomposition products, including possible technology of luminescent contrast agents’ application to increase sensitivity of spectroscopic methods and remote determination of toxicants on the ground. Further possibilities to develop next generation materials for protective gear, equipment and multifunctional contact surfaces providing visualization and identification of toxicants and simultaneous catalytic self-decontamination is discussed. Relationship between technologies for improving safety and security at the crossroads of analytical chemistry of warfare agents, criminalistics, chemical safety and pharmaceutics has been demonstrated.

Application of luminescent reagents for detection of toxicants including warfare agents, pesticides and their degradation products and precursors has been systematically reviewed. Methods of organophosphorus toxicants and products of their destruction (OP) detection based on lanthanide luminescent complexes (primarily Eu 3+ ) have the similar sensitivity as the most advanced instrumental chromatographic and biochemical assays with detection level in the range of several ppts that allows to determine supertoxicants at the safety requirements concentration levels and at appropriate analysis duration from a few seconds to 10 minutes. High selectivity of toxicants identification is achieved by means of imprinted materials, modified cyclodextrins and luminescent sensor arrays. This is the basis for development of new technologies for trace analysis of toxicants and their decomposition products, including possible technology of luminescent contrast agents’ application to increase sensitivity of spectroscopic methods and remote determination of toxicants on the ground. Further possibilities to develop next generation materials for protective gear, equipment and multifunctional contact surfaces providing visualization and identification of toxicants and simultaneous catalytic self-decontamination is discussed. Relationship between technologies for improving safety and security at the crossroads of analytical chemistry of warfare agents, criminalistics, chemical safety and pharmaceutics has been demonstrated.

The article describes acute problem - absence of reference standards (Federal Reference Standards) of controlled ingredients of some potent pharmaceuticals (especially narcotic and psychotropic substances) in Russia. Authors present an algorithm for solving this task. According to regulatory documents providing traceability and technical regulation in Russian Federation requires use of the Federal Reference Standards for any official quantitative studies of narcotic and psychotropic substances. Lack of the reference standards does not allow provide: legally meaningful assessment of quality of medical products; to ensure industrial safety of work with substances belonging to list of dangerous goods; to conduct quantitative forensic analysis using instrumental methods, etc. Development of the Federal Reference Standards should be organized in the framework of technological cooperation of organizations (laboratories) which has necessary licenses. Production of the highest quality standards should be organized on a specialized facility where Federal S&T Center Inversiya has already made Federal Reference Standards of toxic chemicals. Creation and introduction in practices Federal Reference Standards of the controlled substances will provide scientific, technical and methodological foundations in development and implementation technologies for production of potent pharmaceutical ingredients in Russian Federation and solutions in the field of criminology and chemical safety and security.

The article describes some approaches to choice of the most potent non-narcotic analgesics among agents investigated in various R&D stages. Preparations non-narcotic analgesics for relief of severe and moderate pain are relatively new area of pharmaceuticals. Their application is very important as an alternative to opiates. However, the actual number of drug candidates is very limited. As a result of the authors analysis one of the most potent non-narcotic analgesics (PNS neurons sodium channel blocker) - Tetrodotoxin (TTX) was recognized as the most promising. Currently FSUE «GosZMP» conducting preclinical studies of injectable preparation of TTX.

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.

A survey is presented for the most common analytical methods, probe sampling methods, and derivativization techniques in measuring the content of organophosphorus toxicants at environmental sites. The major metrological features of measurement techniques for the analytical chemical monitoring of the destruction of chemical weapons are presented.

Представлены наиболее распространенные аналитические методы, способы пробоотбора и приемы дериватизации, реализованные в методиках измерений содержания ФОВ в объектах окружающей среды. Приведены основные метрологические характеристики методик измерений, используемых для химико-аналитического контроля процессов уничтожения химического оружия.The most common analytical techniques, sampling methods and derivatization procedures, implemented in organophosphate chemical agents concentration measurements for environments are presented. The main metrological characteristics of measurements methods which are applied for the purposes of chemical and analytical control over chemical weapons destructions processes are given.

Рассмотрена методическая база химико-аналитического контроля на объектах по уничтожению химического оружия. Информационная основа данной базы - отдельный раздел «1-ХО» Федерального реестра методик измерений, являющийся частью Федерального информационного фонда по обеспечению единства измерений. Методическая база основана на анализе проектно-технологической документации объектов по уничтожению химического оружия и является результатом исследований в сфере химического разоружения, проводимых в течение последних одиннадцати лет, в частности в ФНТЦ «Инверсия».The paper contains analysis of methodological basis of chemical and analytical control over chemical weapon destruction facilities. Information background for this methodological basis is the separate section of «1-CW» State register of measurement methods which is the part of State information foundation providing uniformity of measurement. Methodological base was created according to analysis of project design documentation for chemical weapon destruction facilities. It is the result of investigations in the field of chemical disarmament which have been carried out for the last 11 years, in JSC SSRMC «Inversiya» among them.

Basic methods were examined for analytical chemical monitoring at chemical weapons facilities. The database for this monitoring is found in a separate section 1-KhO of the State Register of Measurement Methods, which is part of the Federal Information Foundation for the Assurance of Measurement Uniformity. These monitoring methods are based on analysis of the project design documentation of chemical weapon destruction facilities and have emerged from investigations in chemical weapon disarmament over the past 11 years, in particular, at the Inversiya Technology Center.

Разработана методика раздельного определения микроколичеств иприта (2,2-дихлордиэтилсульфида) и -люизита (2-хлорвинилдихлорарсина) в битумных массах, образующихся в процессе битумирования ипритно-люизитных реакционных масс на объектах уничтожения химического оружия в диапазоне концентраций (2–20) ? 10-4 %.

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 is developed for the separate determination of microquantities of iprite (2,2′-dichlorodiethylsulfide) and α-lewisite (2-chlorovinyldichloroarsine) in bituminous masses formed in the bitumenation of iprite-lewisite crude mixtures in objects of the destruction of chemical weapons. The concentration range is (2–20) × 10−4%.

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.