The article examines the role of ubiquinone as a redox molecule whose functions consist in electron transport in the mitochondrial respiratory chain and regeneration of endogenous antioxidants. Changes in electron redox pathways cause uncontrolled release of reactive oxygen species, which leads to oxidative stress and development of pathologies. The objective of the study was to determine the content of coenzyme Q10 and its redox status in the human body as a biomarker of oxidative stress in various pathologies. This was achieved by assessing and consolidating data on changes in concentrations of the oxidized, reduced ubiquinone forms and total ubiquinone in various pathologies. Total serum ubiquinone was reduced in patients with chronic heart failure (0.68 μmol/L) compared with the control group (0.97 μmol/L). The redox status, expressed as the [ubiquinol]/ [ubiquinone] concentration ratio, decreased in patients with coronary heart disease (0.49 ± 0.34), diabetes (0.26 ± 0.16) compared with the healthy subjects (1.23–1.41). A negative correlation with malonic dialdehyde was observed. The authors analysed the possibility of assessing the efficacy of statin therapy by plasma ubiquinone concentration in patients. Patients with hyperlipidemia who received statins showed a statistically significant reduction in ubiquinol concentration after taking the drug (from 0.81 to 0.46 μg/mL) and the [ubiquinone]/[total ubiquinone] ratio (from 11 to 10 %), which confirms the potential mechanism of statinassociated muscle injury development. Thus, coenzyme Q10 redox status, as well as the concentrations of oxidized, reduced and total ubiquinone can be effective biomarkers of oxidative stress in cardiovascular diseases, diabetes, as well as an important indicator in evaluating the efficacy of hyperlipidemia treatment.

One of the prerequisites of efficacy and safety of finished pharmaceutical products is the quality of pharmaceutical substances used in their production. Criteria of assessment of pharmaceutical substance purity are determined by the substance composition and production technology, as well as by specific aspects of the finished pharmaceutical product production and use. It is necessary to control the content of nonspecific organic and inorganic impurities, impurities of microbial origin, and residual solvents. The aim of the study was to analyse characteristics of test methods used to determine nonspecific impurities in pharmaceutical substances. The State Pharmacopoeia of the Russian Federation describes various chemical, physical, physicochemical and biological tests for the analysis of nonspecific impurities. Determination of inorganic cations and anions usually includes comparison of test solutions with solutions of the corresponding reference standards, or checking the absence of a positive reaction in the test solution. Quantitative analysis of trace impurities largely relies on highly specific and sensitive test methods, such as atomic absorption spectrometry, atomic emission spectrometry and inductively coupled plasma mass spectrometry. The content of residual organic solvents is determined by gas chromatography or high-performance liquid chromatography. The purity and safety of pharmaceutical substances are ensured by biological tests: “Microbial quality”, “Sterility”, “Pyrogenicity”, “Bacterial endotoxins”. Specific characteristics of test methods used for determination of the content of nonspecific impurities in various pharmaceutical substances depend on physicochemical properties of the tested substances, toxicity of the analysed impurities, and content limits. The results of the study make it possible to formulate a methodological approach to the development of criteria for assessing the quality of pharmaceutical substances. This approach includes mandatory compliance with the basic principles of substance standardisation, as well as case-by-case selection of quality parameters, specific test conditions and content limits for impurities.

Spontaneous preterm birth is one of the most pressing issues in obstetrics, as it remains one of the leading causes of newborn morbidity and mortality. Pending issues of aetiology, pathogenesis, and absence of medicinal products indicated for the treatment of spontaneous preterm labour pose a challenge for rational pharmacotherapy. The paper presents the results of a scientific literature review on the problem of rational pharmacotherapy of spontaneous preterm labour using tocolytic drugs — calcium channel blockers, cyclooxygenase inhibitors. The paper summarises specific pharmacokinetic parameters of these drugs during pregnancy. It discusses pharmacogenetic aspects of using tocolytic drugs in pregnant women and their potential clinical effects. It was demonstrated that women with threatened miscarriage had high interindividual variability in nifedipine plasma concentrations depending on CYP3A5 genotype. It was shown that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic rate and an increase in indomethacin clearance resulting in the reduction of its efficacy. Yet, there is minimal research regarding this issue. Therefore, further research is needed to assess the impact of CYP3A5 and CYP2C9 genotypes on the efficacy and safety of nifedipine and indomethacin used as tocolytic drugs in obstetrics.

Algae tend to accumulate elemental toxic substances in high concentrations. Algae are widely used in the food and pharmaceutical industries, and this dictates the need to establish limits for the content of toxic substances that they may contain. The aim of the study was to analyse the requirements of the Russian and foreign pharmacopoeias and other regulatory documents concerning the limits for the content of arsenic in brown algae. The paper presents the results of analysis of monographs from the State Pharmacopoeia of the Russian Federation, XIII and XIV editions, draft version of the Pharmacopoeia of the Eurasian Economic Union, United States Pharmacopoeia, Japanese Pharmacopoeia, European Pharmacopoeia, and Ayurvedic Pharmacopoeia of India containing limits for the content of arsenic in herbal medicinal products (HMPs). In addition, the authors analysed Russian, international and foreign food industry and dietary supplements regulations, as well as scientific publications on arsenic content in brown algae. They also considered the nomenclature of arsenic compounds to be determined and controlled in medicinal products, highlighted the main approaches to and identified global trends in establishing the limits for their content in HMPs. The paper summarises specific aspects of inorganic arsenic compounds accumulation by brown algae. It was demonstrated that the majority of foreign pharmacopoeias either have specific norms for arsenic content in brown algae, which differ from the norms for HMPs, or have general norms that take into account different toxicity levels of organic and inorganic arsenic compounds. There is a tendency to control the content of elemental toxic substances based on their maximum allowable daily intake. The paper substantiates the need for separate determination of toxic inorganic arsenic compounds and potentially toxic methyl arsonate and dimethyl arsinate in HMPs.

Cefepime (active substance ‒ cefepime dihydrochloride monohydrate) is a fourth-generation antibiotic with a broad spectrum of action. The study of the chemical and toxicological properties of cefepime is especially relevant because there have been some cases of poisoning with this antibiotic which resulted in a fatal outcome, and because there is a lack of simple and up-to-date methods of its determination.

The study objective was to select conditions for cefepime extraction from biological material for subsequent use in forensic examination.

Materials and methods: the determination of conditions for cefepime extraction from biological material was performed using model mixtures and included selection of an adequate extracting agent and the required amount of the agent, as well as selection of the duration and number of digestion steps. Identification, purification and quantification of cefepime were performed using thin-layer chromatography and spectrophotometry methods.

Results: an acceptable agent that could be used for cefepime extraction from biological material is an acetone-water mixture (1:1), the amount of the extracting component should be twice the amount of the biological material, the time of contact between the extracting agent and the biological material should be at least 30 minutes.

Conclusions: the results of the study allowed us to identify an acceptable extracting agent and the conditions for cefepime extraction from biological material for identification and quantification of the antibiotic during forensic examination.

The process of harmonisation of Russian and foreign approaches and requirements in the field of medicines quality assurance calls for revision of quality control procedures included in various regulations and guidelines. The monograph FS.2.5.0062.18 “Hawthorn flowers” of the State Pharmacopoeia of the Russian Federation XIV edition includes a test procedure for determination of flavonoids by a chromatospectrophotometric method. This procedure does not take into account current scientific capabilities and has a number of shortcomings, therefore it was necessary to revise the existing test procedure and develop a new approach to the standardisation of the hawthorn flower herbal substance.

The objective of the study was to develop an assay method for standardisation and evaluation of hawthorn flower using high performance liquid chromatography (HPLC).

Materials and methods: the study was performed using samples of hawthorn flowers by Russian manufacturers. Quercetin (USP RS) and Hyperoside (HWI, primary standard) were used as the reference standards. The HPLC analysis was performed using an Infinity II 1260 DAD LC system (Agilent), and the UV spectra were recorded on a Cary 100 Varian spectrophotometer. A TLC Visualizer (CAMAG) was used to obtain digital images of thin layer chromatography plates.

Results: the authors developed an HPLC test procedure for quantitative determination of total flavonoids, expressed as hyperoside, in hawthorn flowers. The developed procedure gives reliable and reproducible results and is characterised by high sensitivity and selectivity. The results of quantitative determination of the total flavonoid content in hawthorn flowers were used to propose the standard for the total content of flavonoids, expressed as hyperoside, of “not less than 0.5%”.

Conclusions: the developed assay method for determination of active pharmaceutical ingredients in hawthorn flower products by HPLC can be recommended for inclusion into the Assay part of the “Hawthorn Flowers” monograph of the State Pharmacopoeia of the Russian Federation.

Generic drugs are widely discussed in the scientific literature. Their key advantage is high availability in the medical practice due to the possibility of a significant reduction in developer costs. In most cases the efficacy and safety of generic oral drugs are confirmed based on the acceptable results of pharmacokinetic evaluation of their bioequivalence with the reference drug. However, generic drugs are not directly compared with one another, and this calls into question the validity of the conclusion about the interchangeability of the generic drugs.

The aim of this study was to evaluate the results of indirect comparison of generic drugs by the ratios of their AUC_0-t and С_max based on the information obtained in bioequivalence studies involving the reference drug.

Materials and methods: the authors performed an indirect comparison of the results of bioequivalence studies of generic drugs containing one active pharmaceutical ingredient. The analysis was based on bioequivalence study reports over the last 7 years dealing with risk/benefit assessment of imatinib and tacrolimus products.

Results: the results of indirect assessment of 90 % confidence intervals of the ratios of imatinib products’ geometric means show that in 46.7 % of cases the intervals fall outside the generally accepted limits (80–125 %) for at least one of the estimated parameters. As for tacrolimus products, the intervals did not go beyond the generally accepted limits (80–125 %) for the AUC_0-t  ratio, but a discrepancy was found in 10 % of cases for the C_max ratio. However, when narrower limits of 90–111 % were used to assess the AUC_0-t ratio, 90 % of the compared pairs did not meet the recommended standards.

Conclusions: thus, conclusions on the acceptable degree of bioequivalence of two generic drugs to the reference product cannot constitute a scientifically sufficient reason for regarding these generic drugs as clinically equivalent.

Improvement of drug supply is one of the key factors contributing to the quality of medical services, but it cannot be achieved without introduction of digital technologies. This is a complex task that requires a systematic approach which includes planning, design, development, implementation and operation of information systems.

The purpose of this study was to develop and test a procedure for assessing the effectiveness of information systems supporting medicines evaluation.

Materials and methods: the paper analyses Russian and foreign scientific publications devoted to the assessment of effectiveness of information systems implementation. The author conducted a system analysis using the procedure for constructing a model of a data processing system.

Results: the analysis of literature sources helped to determine methods that could be used to assess the effectiveness of information systems implementation. The «Document management — Medicines evaluation» system was used to construct a model system, and the analysis of the system’s effectiveness made it possible to propose ways for further improvement.

Conclusion: the analysis of the literature sources demonstrated that the use of digital modelling methods helps to assess the effectiveness of information systems supporting medicines evaluation. The paper analysed the «Document management — Medicines evaluation» system used for receipt and registration of medicine samples. This system makes it possible to preplan the order in which applications will be received and rule out the possibility of simultaneous receipt of several applications. Based on the results of the analysis it is suggested that an additional receiving point should be set up in order to improve the throughput of the system.

Preclinical safety evaluation is an important stage in the development of medicinal products. Clinical laboratory studies, including haematological, biochemical and pathomorphological studies, are an essential part of chronic toxicity studies. A careful choice of methodological approaches to examination of toxicological characteristics of drug candidates makes it possible to assess the degree of risk associated with their subsequent clinical use, identify potential target organs, determine the extent of damage, as well as the possibility and dynamics of restoring damaged systems. Key prerequisites for obtaining adequate results of the studies are correct methodological implementation of all the stages of sample preparation and careful consideration of all factors during interpretation of the obtained data. Thus, the choice of methodological approaches to blood tests is often determined by the species, age and sex of laboratory animals, as well as by specific characteristics of the tested drug. The aim of the study was to summarise data on haematological studies performed in the Drug Toxicology Laboratory of the Federal State Budgetary Institute «Zakusov Institute of Pharmacology» when conducting chronic toxicity studies.