Introduction. In recent years, interest in the compounds of the benzofuroxane series has increased, because they have a wide range of biological activity, and in addition are donors of nitric oxide. In the scientific literature, many works are related to the synthesis and study of the biological activity of 5-nitro-4,6-dichlorobenzofuroxane amino derivatives, whereas amino derivatives of the 5,7-dichlor-4,6-dinitrobenzofuroxane substrate have been poorly studied.

Aim. Is the synthesis of new amino derivatives of 5,7-dichloro-4,6-dinitrobenzofuroxane and the study of their biological activity.

Materials and methods. Investigated the reaction of condensation of 5,7-dichloro-4,6-dinitrobenzofuroxane with different aromatic amines, containing functional groups of acceptor character in their structure were selected. In order to increase the yield for each specific reaction, the reaction conditions were selected (the reaction temperature, medium, and the amount of amine). The structure of the compounds confirmed IR, NMR spectra and elemental analysis.

Results and discussion. New compounds in the 5,7-diamino-4,6-dinitrobenzofuroxane series were obtained. Acute toxicity, acaricidal and bacteriostatic activity against Escherichia coli and Staphylococcus aureus were studied. The obtained compounds were found to have high pharmacological activity, superior to the comparison drug (Chlorophos and Creolin).

Conclusion. Most of the amino derivative synthesized 5,7-dichloro-4,6-dinitrobenzofuroxane have a high activity against mites and bacteria. Compounds containing in their structure chlorine and methyl radicals, have biological activity at low concentrations, are low-toxic and belong to the 4th hazard class.

Introduction. Employees of the Department of Pharmaceutical Chemistry and Pharmaceutical Technology have obtained modified forms of terpino-indole alkaloids (ТIA) and vinbristine (VCR) and vinblastine (VBL) known in the treatment of cancer diseases by incorporating them into the erythrocyte carriers (EN) by the modified method of hypoosmotic lysis in the modified (aprotic solvent dimethyl sulfoxide (DMSO) and polyethylene glycol (PEG 4000) and unmodified media.

Aim. The aim of the work was to study the desorption and release of terpene-indole vincristine and vinblastine alkaloids from previously obtained cellular erythrocyte carriers.

Materials and methods. In the experiment performed, the release characteristics of encapsulated preparations from erythrocytes were determined. TIA preparations were released from erythrocyte form in 6 hours: VCR – 54.5305%, VCR : PEG-4000 (1:5) – 53.3305%, VCR : PEG-4000 (1:10) – 40.1283%, VCR : PEG-4000 (1:20) – 39.9869%, VCR : DMSO (2 mg/ml) – 54.2354%, VBL – 68.0656%; VBL : PEG-4000 (1:10) – 63.8941%; VBL : PEG-4000 (1:20) – 60.7455%; VBL : PEG-400 (1:20) – 60.3529%; VBL : DMSO (2 mg/ml) – 64.5006%. The rate of release from an erythrocyte form encapsulated in a medium modified with DMSO is significantly higher than that encapsulated in an unmodified medium. The average rate of TIA release from erythrocyte forms encapsulated in PEG medium is approximately the same.

Results and discussion. The results show that the release of hemoglobin from TIA encapsulated erythrocytes compared with non-encapsulated EN is small. The results show that, on average, 8.242 ± 0.3135% of hemoglobin is released from TIA encapsulated with EN, compared to control erythrocytes – 7.53% after 6 h of incubation at 37 °C. The release of hemoglobin from the TIA of encapsulated erythrocytes in modified media is less than that encapsulated in unmodified medium.

Conclusion. Based on these results, it can be suggested that PEG can bind to the erythrocyte membrane and stabilize it.

Introduction. Influenza and acute respiratory viral infection (hereinafter – ARVI) are serious diseases that affect up to 500 million people worldwide every year. From 27.3 to 41.2 million people are registered annually in Russia. Thus, the urgent task is to develop new effective drugs aimed at the prevention and treatment of the above diseases. The drug composition for intranasal use based on aminocaproic acid with antiviral activity and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine with a proven immunostimulating action was developed.

Aim. Study of the antiviral activity of the complex drug composition with aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine.

Materials and methods. To reach this goal, preparations with different ratios of active substances were used to identify the best efficacy. The study was conducted in comparison with the known drug zanamivir. Antiviral activity was studied against influenza A/Puerto Rico/8/34 (H1N1) virus in white outbred mice upon nasal administration of the test samples. The activity evaluation of the studied drugs was carried out according to the weight values and the death dynamics control and experimental groups of animals. Infectious activity of the virus in the lung tissue of animals was assessed on day 5 after infection by titration on a culture of MDCK cells in a nutrient medium MEM. Virus titer was expressed in logarithm of 50% of the virus experimental infectious dose (lg TCID₅₀) per 200 μl of medium.

Results and discussion. Based on the data obtained during the study of the weight values dynamics and the dynamics of animal death, the drug showed a maximum antiviral activity with a 2:1 ratio of active substances, which is confirmed by the data on viral activity in the lungs of animals, the virus titer was 1.9±0.3 (p=0.616) lg TCID₅₀/0.2 ml.

Conclusion. Antiviral activity of the complex preparation based on aminocaproic acid and N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymer was studied, the most effective ratio of active substances was found, it is 2:1. Thus this complex preparation with a ratio of active substances 2:1 reduced the viral load level in the lung tissue of infected mice by more than two times relative to the control group. Therefore, this combination of active substances can be used to develop a promising drug for nasal use as treatment and prevention of influenza and ARVI.

Introduction. Naftifin hydrochloride is an antifungal drug from the allylamine group, which is used as a drug for external use in the treatment of onychomycosis. Quickly penetrates the skin and nails. It has antifungal, antibacterial and anti-inflammatory effects. It has a wide range of actions against many fungi that cause onychomycosis (dermatophytes, molds and yeast). In addition, it has an antibacterial effect in the ratio of gram-positive and gram-negative bacteria, reduces the risk of complicated course of the disease. It has a pronounced anti-inflammatory effect. Polyethylene glycols belong to the class of organic polymers of ethylene glycol. Polyethylene glycols are safe and widely used in pharmaceutical production, due to the variety of applications. The object of the study is a number of solutions of naftifin hydrochloride in different combinations and with different ratios of polyethylene glycols.

Aim. The purpose of the work is to choose the optimal composition of the solution of naftifin hydrochloride. Achieve due to the viscosity of the prolonging action of the solution. Depending on the molecular weight of polyethylene glycol to determine the flow time of solutions. Choose among a number of samples with different ratios of polyethylene glycols, a solution with maximum viscosity.

Materials and methods. To determine the viscosity of this solution, a capillary viscometry method was used on the vpzh-2 apparatus. «Exoderil» solution was chosen as a reference formulation.

Results and discussion. Alternating different combinations of polyethylene glycol, we have increased the viscosity of the fluid naftifine hydrochloride, which has achieved a more accurate method of application of medicinal substances. During the study, it was determined that the solution «Exoderil» has a minimum viscosity, compared with all samples of the studied solutions.

Сonclusion. The optimal viscosity of the solution of naftifin hydrochloride provides a prolonged action of the drug, due to a longer stay on the nail plate. Viscosity allows for more accurate application to the damaged nail, and reduces the loss of concentration of the active substance. Moisturizing properties of polyethylene glycols will help to reduce the severity of side effects (dryness, rarefaction), and provide a longer and more comfortable treatment of onychomycosis.

Introduction. Substances with sorption properties can be used to create transport drug systems, in which the main mechanism of binding, transport and release of the drug molecule is sorption. The sorbent in this case acts as a carrier of the drug molecule, followed by its delivery to the destination by desorption. One of the ways to study the processes of sorption-desorption in transport drug systems is the study of the morphology of the sorption substance. Therefore, the morphological analysis of sorption substances is important, including the size, shape, and spatial organization of their structural elements.

Aim. The study of the morphology of sorption substances.

Materials and methods. The materials of the study are active coal, silicon dioxide, povidone, dioctahedral smectite, kaolin and montmorillonite clay. The methods is scanning electron microscopy.

Results and discussion. The scanning electron microscopy of objects was carried out using segmentation of elements as subsystems, inside of which the morphological description does not penetrate. It was established that for coal of active and silicon dioxide, the segmentation of elements is represented by three levels of organization; for povidone, smectite, kaolin and montmorillonite clay, the segmentation of elements is represented by two levels of organization. The morphology of the objects was investigated. It is established that the studied substances are microstructural objects. Porosity in samples of active coal, smectite dioctahedral, kaolin, montmorillonite clay was determined. In samples of silicon dioxide and povidone porosity is absent.

Conclusion. Morphological analysis of sorption substances allowed us to develop classification of the possible interaction of the carrier substance with the drug molecule in the transport drug system. The materials under study are divided into two groups according to porous characteristics: group 1 – porous substances – sorption interaction in pores (active coal), sorption interaction in pores and by ion exchange (smectite, montmorillonite clay), sorption in secondary pores and through oxygen and hydroxyl centers (kaolin); group 2 – non-porous substances – sorption on oxygen centers (silicon dioxide), sorption by means of complex formation (povidone). The prospect of further research is the modeling of porosity and sorption interaction of the carrier substance with the drug molecule in the drug transport system.

Introduction. Aspects of the use of nitrofurans for external use (nitrofural, furazolidone and furazidin) are described in the article. Review of current research that is dedicated to development of drugs containing nitrofuran derivatives has been carried out. The prospects for creating dosage forms of furaсillin and furazolidone containing their solid dispersions with polymers are considered.

Text. The group of nitrofurans is widely in demand in the modern pharmaceutical market. The most common active ingredients – furacillin, furazolidone and furazidin are represented by various dosage forms for both internal and external use. All nitrofuran derivatives have a wide spectrum of antimicrobial action and a specific mechanism of action on bacterial cells. The low level of development of antimicrobial resistance allows nitrofurans to remain one of the most effective chemotherapeutic groups of antimicrobial compounds for many decades. The review shows a numerous current developments carried out by both Russian and foreign authors about use of furacillin, furadonin and furazidin to develop the composition of new drugs, including combination drugs, as well as promising treatment methods. Currently, on the basis of Sechenov University, research is actively conducted to increase the solubility and dissolution rate of nitrofurans in water using the method of solid dispersions. Also, work is underway to develop the composition and technology of solid (instant) dosage forms granules and tablets, and soft dosage forms gels containing furacillin and furazolidone as active substances.

Conclusion. Despite the use of active substances from the nitrofuran group in pharmaceutical practice for more than half a century and their low solubility in water, research on the development of complex drugs for external use and mono-preparations of nitrofurans have not lost their relevance and are actively conducted to this day.

Introduction. Due to the growth of general surgical diseases, the treatment and cessation of bleeding is an important problem of medicine and pharmacy. The existing range of hemostatics does not always meet the needs of medical practice and does not provide a wide choice of drugs. Given the great need for drugs to stop bleeding, their development is an urgent task for the modern pharmaceutical industry. One of the promising areas of the creation of dosage forms is the development of hemostatic ointment. Soft dosage forms with optimal rheological characteristics are characterized by a good degree of spreading and easy extrusion of tubes. In the present work, the composition and technology of hemostatic ointment with a nanocomponent was proposed.

Aim. Justification of the optimal composition by studying the rheological parameters and the development of technology for producing a soft dosage form with nanoparticles to stop bleeding.

Materials and methods. The pharmaceutical substance was aminocaproic acid (FS.2.1.0001.15), iron III chloride (GOST 4147-74), iron oxide nanoparticles (GOST R 57909-2017). The nanoparticles used in this work were obtained by a levitation jet method in a carrier gas medium. The work used technological, physical and chemical research methods. The method of rotational viscometry on the instrument Haake VT550 viscometer is described methodically in detail. Statistical processing of the results was carried out according to the GF XIV methods using standard computer programs.

Results and discussion. As a result of the study, it was found that the viscosity of the ointment samples studied gradually decreased with an increase in shear rate, but was non-linear. This dependence is characteristic of systems with a plastic type of flow and characterizes the samples under study as a structured dispersed system. It was also found that the samples of the soft dosage form had thixotropic properties. This in turn serves as an indicator of good lubrication and extrusion of tubes.

Conclusion. A production technology has been proposed and a technological scheme for the production of a hemostatic soft dosage form with nanoparticles has been designed.

Introduction. The fixed combination of ketoprofen, methyl salicylate and levomenthol in the form of a cream-gel is rational. Ketoprofen forms salts with bases and esters with substances containing hydroxyl groups. Ketoprofen is practically insoluble in water, and the solubility of ketoprofen salts is much higher; this can lead to its different localization in the o/w emulsion and affect the profile of ketoprofen impurities resulting from esterification.

Aim. The aim of the work is to study the effect of ketoprofen distribution in cream-gels on the formation of the impurities during storage.

Materials and methods. Cream-gels with pH of 5,5 or 6,8 containing ketoprofen 2,5%, levomenthol 5% and methyl salicylate 10% have been studied. For their production, ketoprofen was dissolved in the mixture of levomenthol – methyl salicylate or in the mixed solvent of water – propylene glycol (PG) – diethylene glycol monoethyl ether (DGME). The impurities have been identified by liquid chromatography and the distribution of ketoprofen between the phases of the emulsion and the content of impurities in cream-gels have been determined by the same method. The rheological characteristics of cream-gels have been studied by viscosity-rotating viscometer method, and their microstructure – by optical microscopy.

Results and their discussion. The formation of ketoprofen esters with PG, DGME and levomenthol in cream-gels have been studied. Differences in the localization of ketoprofen in the phases of the o/w emulsion at pH 5,5 and 6,8 have been shown. The formed impurities have been identified by the retention times of their peaks on chromatograms, by UV spectra and mass spectra. It has been established that during storage the content of ketoprofen esters with PG, DGME and levomenthol increased, but their formation rate was lower at pH=6,8 as well as at the adding of ketoprofen as a salt with trometamol into the dispersion medium of cream-gel. However, this resulted in formation of three impurities that were identified by UV spectra as decomposition products of methyl salicylate. When storing cream-gels with pH=6,8, the content of decomposition products of methyl salicylate, which were not detected at pH=5,5, increased.

Conclusion. When making a cream-gel, ketoprofen is advisable to dissolve in a mixture of methyl salicylate and levomenthol and standardize the pH about 5,5. It is rational to use hydrophilic solvents without hydroxyl groups as penetration enhancers and the impurity profile could be limited to the menthol esters of the enantiomers of ketoprofen as a result.

Introduction. Liposomal technologies are widely used in medicine and cosmetology as a delivery system for diagnostic and medicinal products and biologically active substances. The undoubted practical importance at the stage of development of a liposomal preparation is represented by the characteristic and assessment of the sustainability of the obtained product, and special attention is paid to the study of the latter. Essentially, the methods for their preparation affect the stability of liposomes; therefore, the study of the influence of technological factors on the properties of the product at various stages of the preparation of liposomes is very important. This article is devoted to the study of the dependence of the quality of liposomes loaded with a phthalocyanine photosensitizer – thiosens, on the conditions of their production.

Aim. Detection of the influence of various technological factors on the stability indicators of the liposomal form of the thiosens photosensitizer.

Materials and methods. For this purpose, an analysis of the average size, polydispersity and zeta (ζ) potential of the liposomes of thiosens obtained at the stage of hydration of the lipid film, filtration of the liposomal dispersion, its extrusion, homogenization, ultrasonic treatment, and lyophilization was carried out.

Results and discussion. During the preparation of a liposomal preparation, various changes in conditions can be made within the framework of the technological process. At each stage of obtaining a liposomal form, there are many critical points and parameters that must be strictly monitored and controlled. In the course of the work, the influence of technological factors on the stability of liposomal intermediate and finished products was assessed. The conditions of the most effective hydration with the formation of a stable dispersion of multilayer liposomes of thiosens and the optimal method of their grinding have been determined. It was also shown that liposomes formed after rehydration of the lyophilisate are more uniform in size and have the highest ζ-potential value in comparison with non-lyophilized liposomal dispersion.

Conclusion. Using the example of a thiosens phthalocyanine photosensitizer liposomes, the influence of various technological factors on the stability of this nanostructure is shown, therefore, the characteristic and assessment of the sustainability of the resulting product according to 3 main indicators – vesicle size, polydispersity index, and ζ-potential are of undoubted practical importance.

Introduction. In this research is devoted to questions of development of structure and technology of granules of an omeprazole. It is established that the most optimal dosage form for medicines of inhibitors of a proton pump is considered to be the tablet with a multiple-unit pellets system (microparticles). In this case of the production of these medicines in the microgranules of a particle are covered with several protective covers. For development of microgranules of an omeprazole is offered the technology of lamination in the fluid bed apparatus.

Aim. To receive in the fluid bed apparatus of the microgranules of an omeprazole covered with the enteric cover.

Materials and methods. To solve this problem technical characteristics on the granulates of an omeprazole received at various operating modes of the fluid bed apparatus are defined such as form of granules, fractional structure and bulk density are determined by the methods described by the State Pharmacopeia of the XIII edition.

Results and discussion. As a result of a research the choice of polymers for layered deposition in the granulation process of a substance of omeprazole is substantiated. Produced selection of enteric polymer of various firms of producers is made for providing a necessary profile of release of an omeprazole in a human body. A copolymer of methacrylic acid – Kollicoat MAE 100 P is chosen. Special attention is paid to receiving the enteric granules of an omeprazole of the correct spherical form with minimum roughness and the improved flowability for further tabletting. For the purpose of receiving granules of an omeprazole of a spherical form selection of an optimum operating mode of the device of a fluid bed apparatus is made for implementation of process of applying the enteric polymer. Following the results of experiments the dependence of quality of fractional structure and appearance of granules of an omeprazole on temperature, pressure and feed rate of polymer is defined. Besides, it is established that the uniformity of application and thickness of a layer of the applied enteric polymer on granules of an omeprazole depend not only on the polymer feed rate, but also on the size of drops of the feed solution.

Conclusion. It is established that the quality of the granules of an omeprazole received the enteric polymer was affected by such factors of technological parameters of the fluid bed apparatus as: temperature of the entering air in the apparatus, the air pressure upon a nozzle, air pressure upon a gas-distributing grid of the apparatus, speed of the given polymer, a lot of loading of granules, air temperature of a layer of granules, duration of drying of granules upon termination of process of application of the enteric polymer.

Introduction. Common sorrel (Rumex acetosa L.) is a biennial herb from the Buckwheat family (Polygonaceae L.). In our previously studies of phenolic compounds composition of alcohol extraction and ethereal, ethyl acetate, butanol fractions of common sorrel herba and flavonoids of the flavonol group was found. From the literature sources it is known that flavonoids are one of the groups of biologically active compounds with anti-inflammatory action. In this regard, the actual task is to assess the quantitative content of flavonoids in common sorrel herba.

Aim. Is the development and validation of a method for the quantitative determination of flavonoids in common sorrel herba.

Materials and methods. It has been established that the flavonoid complex of common sorrel herba includes rutin, therefore, the reference sample (RS) rutin was used as a standard for calculating the amount of flavonoids. Alcohol extract of common sorrel herba and a solution of rutin RS were prepared. The complexation reaction with aluminum chloride was carried out. The resulting solutions were investigated by the method of differential spectrophotometry. The spectral characteristics of the test and standard samples were compared. Then we studied the effect of extraction conditions on the yield of flavonoids from the raw material: the extractant, the particle size of the raw material, the ratio of «raw material – extractant», temperature, frequency and duration of extraction. Purified water and ethyl alcohol of various concentrations (20%, 40%, 70%, 90%) were used as the extractant. Next, carried out the selection of the optimal conditions for the complexation reaction (the complexation reaction time, the ratio of «aliquot – aluminum chloride alcohol solution»). The method was validated according to GPM.1.1.0012.15 of the State Pharmacopoeia (SF) XIII edition and generally accepted methods for the following indicators: specificity, analytical field, linearity, accuracy, precision.

Results and discussion. The optimal parameters for extracting flavonoids from raw materials were determined (threefold extraction with ethyl alcohol 70% in a water bath, the ratio of «raw material – extractant» – 1:30 for 30 minutes, the particle size of the raw material – 2.0 mm). The conditions for the complexation reaction were selected (the ratio «aliquot: aluminum chloride alcohol solution» – 1: 2.5, the complexing agent – aluminum chloride solution 5% alcohol, the appearance of a stable solution color after 40 minutes). When carrying out the validation of the developed method, it was established that the validation characteristics under study are within the acceptance criteria. When analyzing the raw materials harvested in the Altai Territory in different years, it was found that the content of flavonoids in common sorrel herba ranges from 0,596 to 0,632%.

Conclusion. The optimal parameters of extraction of flavonoids from raw materials were determined, the conditions for the complexation reaction were selected, and the developed method was validated. The quantitative content of flavonoids in terms of rutin in sorrel sour grass harvested in the Altai Territory in different years has been established.

Introduction. The actual form of packaging licorice roots for water extraction are filter paper sachets. New forms of licorice root processing provide the proper technological properties of raw materials for filter paper sachets.

Aim. A comparative assessment of the of glycyrrhizic acid (GA) content in licorice roots (LR), produced in the Russian Federation and in licorice raw materials of various processing methods by HPLC-UV.

Materials and methods. The objects of research were crushed LR, packaged in packs of industrial production and laboratory-industrial samples of coarse powder (CP), cut-pressed granules (CPG) and compositions proposed for packaging in filter paper sachets. The determination of GA content was carried out on an Agilent 1200 high performance liquid chromatography system equipped with a photodiode array detector (Agilent Technologies, USA). The stationary phase is column Phenomenex Luna® C18(2) 250×4.6 mm. The composition of the mobile phase – 5% orthophosphoric acid water solution: acetonitrile (60:40). A flow rate – 1.0 ml/min, isocratic elution mode. The temperature of the column – 30 °C. The sample injected volume – 10 µl. Detection was performed at a wavelength of 254 nm; run time – 15 minutes.

Results and discussion. The GA content in CP, CPG and the composition of CP and CPG –was determined in the ratio of 80:20 (composition). It was established that the GA content varies in the LR in the range – 7.08–9.17%, CP – 3.87–3.90%, CPG – 6.88–7.08%, and the composition – 4.44–4.88%.

Conclusion. The use of HPLC-UV method for the standardization of licorice roots of domestic production and the roots of various forms of processing is very promising. The technique can be recommended for inclusion in the State Pharmacopoeia of the Russian Federation of a subsequent edition, which will allow harmonizing the quality requirements of domestic licorice raw materials with the requirements of foreign pharmacopoeias.

Introduction. The chemical composition of plants depends on the elemental composition of the habitat, and also reflects the species and individual characteristics of the plant. Before using any plant for medicinal purposes, it is also necessary to collect as much information as possible about the elemental composition of the feedstock.

Aim. Consequently, it became possible to create a method for the rapid determination of trace elements in plants using the X-Ray fluorescent method.

Materials and methods. In accordance with the international intercalibration standard in the IAEA system (IAEA-433), an international standard sample NIST SRM 2976, certified by the National Institute of Standards and Technology (USA), was used to provide external quality control (QA/QC) of laboratory elemental analysis. For Zn the results of plant raw powder materials analysis by XRF (express analysis) were compared with AAS by electrothermal atomization and Zeeman background correction after microwave acid mineralizationof biomaterials. To ensure the reproducibility of the results of XRF-express analysis, it is absolutely necessary to carry out mild drying and dispersion of the plant material.

Results and discussion. The results of X-ray fluorescence (XRF) analysis of the elemental composition of the fruits (fructus Anethi graveolens L.), the seeds (semina Cucurbitae pepo L., semina Menthae arvensis L., semina Cucumis sativa L., semina Kalanchoës daigremontianae) and leaves (folia Callisiae fragrantis L.) of medicinal and nonoficinal plants are presented in the article. The methods of XRF and AAS analysis have been developed for the technology of essential micoelements enrichment in of Callisiae fragrantis control leaves at different ratios of hydrogen isotopologues (D/H) in the water.

Conclusion. For example, zinc(II) has demonstrated the ability to create modified plants with high content of essential microelement, up to 1.4 mg /g dry weight.

Introduction. There is steady upward trend in demand for herbal formulation necessitates the expansion of their range. Recent studies have shown that one of the promising research direction is the development of herbal collection based water-soluble dry extracts. Pectoral species № 4 is one of the most popular among multi-component herbal preparations on the Russian pharmaceutical market. Experimental samples of a dry extract were obtained on the collection basis. According to literature, phenolic compounds predominate both in individual components and pectoral species № 4. Therefore, the end-to-end standardization of the collection and its dry extract by the content of the substances seems to be relevant.

Aim. The present study was performed to examine the dry extract phenolic compounds composition, as well as, to search for marker compounds for the end-to-end standardization of pectoral species № 4 and dosage forms based on it.

Materials and methods. The composition and content of phenolic complex were studied by HPLC with UV detection in pectoral species № 4 and its dry extract. Detection was performed at wavelengths of 350, 300, 270, 210 nm. The quantitative content (%) of the identified compounds was determined by an external standard method.

Results and discussion. HPLC-analysis revealed 58 compounds in pectoral species № 4 and 34 in the extract. Rutin, arbutin, liquraside, liquiritin, quercetin, chlorogenic, caffeic and gallic acid have been identified in all study objects; their quantitative content varied within a range of 0,001−0,910%.

Conclusion. Arbutin, rutin and chlorogenic acid have been proposed as marker compounds.

Introduction. The article presents data of the quantitative mercury determination in an aqueous solution of the pharmaceutical substance protamine sulfate by stripping voltammetry on graphite electrodes modified with a gold-polymer composition. The existing method to determine the mercury impurity in protamine sulfate according to the European Pharmacopoeia – multistage titration with dithizone – is laborious and does not allow to achieve repeatability.

Aim. Analyzing the content of bioaccumulative mercury impurities in a protamine sulfate solution by stripping voltammetry. Materials and methods. Protamine Sulfate Substance (Manufacturer Alps Pharmaceutical Industry Co.Ltd). Experimental data were obtained on a TA-4 semi-automatic analyzer (LLC NPP Tomianalit, Tomsk) with VALabTx software.

Results and discussion. We adapted the method for mercury determination in water and presented the results of its testing on protamine sulfate solution. The results of testing the electrode operation using the «entered-found» method are given, the results of a single mercury analysis were included in the interval 0, 0038–0,0063 mg/l, which confirms their readiness for work. This interval is registered in the methodology and means the limits of permissible deviations. The limits of detection of mercury on the device are 10^-6 –10^-10 mol/l. We prepared a solution with concentrations of 10 mg/m from the protamine sulfate substance and measured it on prepared electrodes. The mercury content in the test sample was 0.00034 mg/l. According to the certificate of protamine sulfate, the mercury content should be ≤10 ppm. We studied the effect in changing of accumulation time. The optimal accumulation time was 80 seconds, because under standard conditions, not all mercury concentrates on the electrode surface, and above 80 seconds there is no significant increase in mercury content.

Conclusion. The proposed method for mercury determination in water by stripping voltammetry on graphite electrodes modified with a gold-polymer composition can be adapted to determine bioaccumulative mercury in the pharmaceutical substance protamine sulfate. The findings suggest that this method can be used in quality control of medicines, as an alternative express method for mercury impurities determination to the existing multistage titration method with dithizone.

Introduction. Tadalafil is a drug used to treat erectile dysfunction. For the quantitative determination of tadalafil in human plasma are used methods of high performance liquid chromatography with ultraviolet and tandem mass spectrometric detection, during the analytical part of pharmacokinetic studies. In the majority of the considered methods the method of liquid-liquid extraction and the method of solid-phase extraction are used, these methods are difficult and expensive. Therefore, the method of protein precipitation was considered as sample preparation. This method is simple and there is important to analysis a lot of clinical samples in bioequivalence studies.

Aim. The aim of this study is to develop method for the quantitative determination of tadalafil in human plasma by HPLC-MS for the analytical part of pharmacokinetic studies.

Materials and methods. Quantitative determination of tadalafil in plasma by HPLC-MS. A sample was prepared using acetonitrile protein precipitation.

Results and discussion. This method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability.

Conclusion. The method of the quantitative determination of tadalafil in human plasma was developed and validated by HPLC-MS. The analytical range of the was 5,00–1000,00 ng/ml tadalafil in plasma. Method could be applied to determination of tadalafil in plasma for PK and BE studies.

Introduction. In the present publication highlights the key points of the main stages of development of methods for determining trace amounts of drugs and metabolites in biological samples using chromatographic and chromatography-mass spectrometry methods. The main sources of errors are specified. The main attention is paid to chromatography-mass spectrometry, which is the basic method of analysis of small molecules in biological samples. Examples from literary sources and authors' own practice are given.

Text. The review highlights some of the practical issues of preparation of calibration samples, method of increasing the stability of the sample at the stage of sampling and plasma preparation. In particular, the influence of various anticoagulants on the accuracy of the analysis is reflected. Specify the method of reducing back conversion of some metabolites of carboxyl-containing drugs to parent compound to prevent overestimation of the results of quantitative determination. Some methods of sample preparation, which have become widespread recently, are noted. For example, solid supported liquid-liquid extraction, based on the extraction of the component of interest from the water sample into the liquid layer distributed on a solid high-polar carrier, followed by eluting by a system of non-polar solvents that do not mix with this layer. Recommendations on the use of internal standards, the preparation of the mobile phase for HPLC, on chromatographic separation, validation techniques are given. In the section «Mass spectrometric detection» features of preparation of a mobile phase for chromatography-mass spectrometry experiments are given. The questions of carry-over reduction, ion suppression, matrix effect are covered. The phenomenon of cross-talk in the study of drug metabolism by chromatography-mass spectrometry is discussed. It consists in the mutual distortion of the mass spectrometric response, when the same mass fragments are formed from different ions-precursors. Features of development of techniques for high-performance pharmacokinetic screening are given.

Conclusion. The authors hope that the presented material will be useful for scientists and specialists in the field of pharmacokinetics, biomarker discovery and clinical analyses.

Introduction. «Linearity» is one of the required characteristics when validating analytical procedures. The issues of the validation of linearity procedures are still relevant.

Aim. To consider the main graphical and calculated criteria for confirmation of the linearity of analytical procedures and their restrictions, as well as to give recommendations.

Materials and methods. Statistical calculations were performed using MS Excel. Experimental data were obtained by HPLC.

Results and discussion. The main criteria for proving/confirming the linearity of analytical procedures and their restrictions are considered in detail. It is shown that these criteria cannot always give a reliable assessment of the linearity of the procedure, the possible reasons for this are indicated and recommendations are given.

Conclusion. When validating the procedures, it is necessary to prove/confirm their linearity by using two, and, more reliably, three criteria, one of which must be the linearity of the plot of measured response (Y) vs concentration of the tested substance (C). On the other hand, we demonstrate here that a formal approach should not be used for the estimation of non-linearity of the procedure when using graphical and calculation criteria based on mathematical statistics, since they do not take into account the possibility of practical insignificance of small deviations from the linear dependence of Y on C.