The manufacturing process, the source (raw materials), and primary packaging materials dictate requirements for the quality of ethyl alcohol used in the pharmaceutical industry.

The aim of the paper was to analyse how the quality of ethyl alcohol used as a component of medicinal products depends on the starting materials, production method and technology, intended use, and the choice of the primary packaging. The paper analyses available information on ethyl alcohol quality and summarises data on potential impurities associated with the ethyl alcohol production technology and the starting materials used. It was established that Russian manufacturers mainly use grain crops (wheat and rye), as well as molasses—a by-product of the sugar industry, as raw materials. The paper addresses the process of improving the quality standards for ethyl alcohol from a historical perspective. A comparative study of the requirements of the Russian and the world’s leading pharmacopoeias for the pharmaceutical substance—ethyl alcohol 95%, 96% demonstrated the need to include identification by IR-spectrometry and impurity control by UV absorbance into the respective monograph of the State Pharmacopoeia of the Russian Federation. The authors formulated requirements for the choice of packaging material for ethyl alcohol, which will not affect its quality during transportation and storage.

One of the major obstacles to effective translational medicine is the challenge of translating animal research results into clinical studies. Scientific literature mainly addresses the selection of the drug dose at initiation of clinical trials (Phase 1). Appropriate selection of doses is also essential for preclinical toxicology and pharmacology studies. Some basic principles that are used when translating dosages from animal models to humans are applicable to selection and justification of doses when planning and conducting preclinical studies. The paper provides an overview of the main methods that can be used for selection and justification of animal doses in preclinical studies, e.g. cross-species dose conversion using body surface area scaling. It summarises situations when doses may be directly converted based on body weight. The paper gives special attention to cross-species dose translation according to pharmacokinetic data. There is no one-size-fits-all approach to cross-species translation; dose conversion must be scientifically justified taking into consideration all information available on the test drug, i.e. its chemical structure, intended route of administration, pharmacokinetic parameters, preclinical and clinical data on pharmacodynamics, and inter-species differences in pharmacokinetics and pharmacodynamics.

The study of the nomenclature of officinal herbal substances and medicinal plants is important for finding potential ways of expanding the existing range of raw materials used in the production of herbal medicinal products. The authors compared the standards included into the State Pharmacopoeia of the Russian Federation, national pharmacopoeias of the Member States of the Eurasian Economic Union, and the world’s leading pharmacopoeias with a focus on herbal substances, medicinal plants, morphological groups of herbal substances, and the proportion of cultivated medicinal plants versus wild medicinal plants. The paper describes historical changes in the nomenclature of herbal substances included in various editions of the Russian Pharmacopoeia. The analysis of the State Register of Medicinal Products revealed the most common morphological groups of herbal substances used in Russia for the production of herbal medicinal products. The paper provides information about the largest Russian manufacturers of herbal medicinal products that preserve national traditions and develop new dosage forms. It outlines ways of improving standardisation of herbal substances using current test methods for characterisation of biologically active substances. The analysis helped to identify potential ways of expanding the range of herbal raw materials: the use of botanical species closely related to officinal ones, increasing the number of morphological groups of substances by integrated use of harvested plants, the inclusion of non-officinal botanical species that have a long history of use in the traditional medicine into the Russian list of officinal species.

The inclusion of requirements for independent determination of arsenic, cadmium, mercury, and lead, and the current sample preparation techniques into the State Pharmacopoeia of the Russian Federation (Ph. Rus.) requires the revision of the existing limits for elemental toxicants in herbal substances and herbal medicinal products produced from them.

The aim of the study was to analyse the data on elemental toxicant content obtained during quality control of herbal substances (herbs, medicinal herb mixtures, extracts, and tinctures) using current test methods and sample preparation techniques, and to compare the obtained results with the Russian and foreign scientific and specialist literature.

Materials and methods: the internal data on the content of critical heavy metals and arsenic in different dosage forms of herbal medicinal products, which were obtained by inductively coupled plasma mass spectrometry after sample preparation by decomposition in closed vessels, were compared with literature data. Results: it was demonstrated that the content of lead, cadmium, and mercury in all the test samples did not exceed the Ph. Rus. limits and was consistent with the analysed literature. The arsenic content in some herbal medicinal products was higher than the established Ph. Rus. limits, but complied with the less stringent Ph. Eur. and USP requirements for herbal substances. The authors investigated the link between the content of elemental toxicants and the place of collection and the part of the plant being tested. It was shown that different types of medicinal plants had a tendency to accumulate particular elements. The authors determined the content of the elements to be controlled in extracts and tinctures. The differences in the Russian and foreign requirements for the content of elemental toxicants may be attributed to the method of obtaining experimental data that form the basis for the setting of limits.

Conclusions: the results of the study confirm the validity of the existing limits for elemental toxicants in herbal medicinal products. The authors demonstrated the need to revise the existing limits for arsenic in herbal medicinal products.

Angiotensin II receptor antagonists (ARAs) are one of the most promising classes of antihypertensive drugs. They are most widely represented on the Russian market by losartan drugs which total 24 items. Therefore, it is crucial to analyse the factors that may affect the results of comparison of generic and reference losartan drugs.

The aim of the study was to perform a retrospective analysis of bioequivalence studies of generic losartan drugs in order to develop approaches to expert evaluation of research protocols and reports.

Materials and methods: the retrospective analysis covered the results of 27 bioequivalence studies of losartan and included the calculation of the pharmacokinetic parameters C_max and AUC_0-t, their intra-individual variability, and the weighted average of intra-individual variability. The calculations were made for the pooled population of men and women, as well as separately for each gender.

Results: the data obtained indicate borderline high variability of losartan in bioequivalence studies (for C_max in 50 % of the studies). It was demonstrated that losartan drugs may have different pharmacokinetics in men and women in terms of C_max and AUC_0-t. The retrospective analysis of the data made it possible to formulate relevant expert approaches to evaluation of protocols and reports of bioequivalence studies of losartan drugs.

Conclusions: Bioequivalence of losartan should be evaluated in three- or four-period, double crossover, two-sequence replicate design studies. The study has to determine the pharmacokinetic parameters of the starting compound and its active metabolite; the period of determination of analytes should be at least 36 hours; the washout period of 7 days is sufficient; blood sampling should be more frequent during the first hour after administration for losartan and during the first 3–4 hours for the metabolite. When determining the sample size, the weighted average of the coefficient of intra-individual variability of C_max of losartan (33 %) should be taken into account. The bioequivalence margins for C_max can be scaled up.

The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.

Materials and methods: ¹H and ¹³C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by ¹H-¹H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.

Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.

Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.