Pharmaceutical Substances Research Articles

Micellar Matrices for Spectrophotometric Determination of 5-Aminosalicylic Acid in Medicinal Preparations Using Response Surface Methodology and Box-Benken Plans

Determination of the content of insoluble pharmaceutical substances in dosage forms is an urgent task, since their dosage is very important for the optimal ratio between the therapeutic effect and ensuring the necessary bioavailability. The use of micellar media as a matrix allows increasing solubility. This report presents the results of the influence of the micellar system consist from cetyltrimethylammonium bromide, CTAB, dimethyl sulfoxide, DMSO and water on the determination of the content of 5-aminosalicylic acid (5-ASA) in pharmaceutical substances and in dosage forms. 5-ASA is widely used for the treatment of inflammatory bowel diseases, ulcerative colitis and Crohn's disease. To obtain the optimal matrix, the methodology of the response surface (MRS) and three-level Box-Benken plans (BBP) were used. The intensity of the absorption band of 5-ASA (A330), which reflects the acid content, was used as the target function. The independent factors were: the concentration of CTAB (pC(CTAB), mol/l); the acidity of medium (pH); the proportion of DMSO in the binary solvent (αDMSO). The BBP consisting of fifteen compositions were compiled and response surfaces constructed. Optimal conditions for the determination of 5-ASA by the absorption band A330 are: pC(CTAB) = 1.1, pH = 7.6, α(DMSO) = 0.3. In this matrix, the content of 5-ASA in the pharmaceutical substance was established and good metrological performance was achieved. The use of MRS and BBP contributes to the development of effective methods for quality control of 5-ASA dosage forms from different manufacturers.

Illegal products containing selective androgen receptor modulators purchased online from Italy: health risks for consumers.

Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding. To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers. Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media. Thirteen SARM products, purchased on retail websites accessible from Italy, were subject to visual inspection and chemical analysis by mass spectrometry and quantitative nuclear magnetic resonance. The primary outcome was demonstration of additional health risks due to the illicit presence of other active ingredients, contamination, and misdosage in SARM products sold on the internet. The secondary outcome was to show the increasing trend of interest in Italy for these products. Most websites reported misleading information; specifically, the statement "for research only" was reported notwithstanding indications on dosage and training phases. The trending search showed that interest toward SARMs increased in Italy in the last years. The use of these products is clearly encouraged by the emerging phenomenon of "broscience" as revealed in socials. Visual inspection evidenced nonconform labeling. Qualitative analysis confirmed the presence of the stated SARM in about 70% of samples. In 23% of samples, the expected SARM was not detected but a different one instead, and in 1 sample, no SARMs were detected. Other undeclared pharmaceutical substances (tamoxifen, clomifene, testosterone, epimethandienone, tadalafil) were measured in 30% of samples. The copresence of >1 active substance was observed in >60% of samples. Quantitative nuclear magnetic resonance data showed nonuniform content ranging from 30% to 90% of the label claim. The use of SARMs, in the presence of unexpected life-threatening reactions in persons using the products to increase sport performance, should be assessed. This investigation involved an integrated approach to study SARM products and related sociologic aspects. The main shortcomings are the limited number of samples and retail websites in the clear web investigated. SARMs sold online as food supplement-like products represent a health hazard due to the presence of unapproved and undeclared active substances. The presence of contaminants clearly indicates the absence of good manufacturing practices in the production, which increases the health risks.

Modern aspects of external application and prospects of using the secretome of mesenchymal stem cells (review)

Introduction. The secretome of mesenchymal stem cells (SMSC) is widely used in medicine. It is most often used due to its immune-modulating and regenerative properties in the treatment of autoimmune, immuno-mediated and other diseases due to its anti-inflammatory, neuroprotective and regenerating action. In many studies, exosomes isolated from SMSC are used as a therapeutic agent. In recent years, the interest in the development of products containing SMSC for external use has increased. Similar drugs are planned to be used in the treatment of diabetic wounds, for skin regeneration, the treatment of inflammatory diseases, as well as alopecia. There are multiple studies on increasing collagen secretion and reducing skin photosensitivity in preclinical studies, which confirms the significant potential for the use of SMSC in dermatology and cosmetology. The purpose of this review was to study the potential of using conditioned medium in medicines for external use, approaches to standardization of SMSC as a pharmaceutical substance and methods of increasing percutaneous delivery.Text. SMSC as an active pharmaceutical ingredient is a transparent liquid from yellow to orange in color with a characteristic odor. The pH of the ready-to-use SMSC composition ranges from 7.0 to 7.5, which allows it to be used in topical and external applications without the addition of stabilizers or pH correctors. Problems of delivery of SMSC through the epidermis are most often solved by placing the secretome in hydrogels, using exosomes or technology using microneedles. Since 2022, after legislative changes, measures have been taken to register and introduce into clinical practice domestic drugs based on cellular products. However, as the analysis showed, it will take some time before the appearance of original medicines based on SMSC, and today in the Russian Federation only products related to cosmetics and veterinary drugs, as well as zoocosmetics, are produced so far.Conclusion. SMSC may also prove to be a safer and more effective substance for the potential treatment of a wide range of acute and chronic diseases. But despite the large number of positive results of using SMSC for wound healing in animals, as well as clinical studies on skin regeneration, there are no studies of its safety and effectiveness, as well as standardization of the production process.

In Vivo Bioequivalence Study of Drug: An Analysis of Bidding in Vietnam Period 2018 - 2022

To promote the development of bioequivalent drugs, the Ministry of Health of Vietnam has classified a separate bidding group for bioequivalent drugs. According to the results of bidding for bioequivalent drugs in the period 2018 - 2022 has achieved very encouraging results, the ratio of domestic bioequivalent drugs compared to foreign bioequivalent drugs winning bids is from 2.13 to 3.63 times higher. Regarding active pharmaceutical ingredients of bioequivalent drugs, bioequivalent drugs with the highest total winning value (including all dosage forms, concentrations,...) focus mainly on antibiotics (cefuroxime, cefixime,…), anti-diabetic drugs (gliclazide, metformin,...), high blood pressure drugs (amlodipine), antipyretic and pain relievers (paracetamol). The winning drug dosage forms are still mainly conventional dosage forms (tablets, film-coated tablets, capsules) and their active ingredients are almost single. In particular, several multi-component bioequivalence drugs have a large total winning value but do not belong to the pharmaceutical group on the list of mandatory bioequivalence test reports when registering the drug, such as the combination of Gliclazide + Metformin; Glibenclamide + Metformin; Glimepiride + Metformin. The trend of selecting pharmaceutical substances/groups of pharmaceutical substances that manufacturers focus on researching/registering bioequivalent drugs in Vietnam is focused on drugs on the list of drugs covered by health insurance.
  

The results of an experimental toxicological assessment of the pharmaceutical substance ambroxol hydrochloride, justification of the maximum permissible content in the air of the working area

Introduction. Ambroxol hydrochloride is a biologically active substance used as a pharmaceutical substance in the manufacture of medicines for secretolytic therapy in the case of acute and chronic bronchopulmonary diseases. To date, there is no hygienic standard for the safe content of substances in the air of the working area in the republic.
 The study aims to substantiate and develop the maximum permissible concentrations and hazard class of the pharmaceutical substance ambroxol hydrochloride in the air of the working area.
 Materials and methods. The authors have conducted experimental toxicological studies of the pharmaceutical substance on animals (rats, mice, rabbits) in accordance with the requirements of technical regulatory legal acts and recommendations of methodological documents regulating the justification of hygienic standards.
 Results. Scientists have found that the pharmaceutical substance ambroxol hydrochloride, when injected into the stomach and inhaled, is classified as a low-hazard substance at an average lethal dose/concentration (according to GOST 12.1.007-76), has a mild irritant effect on the skin and moderate on the mucous membranes of the eyes, does not exhibit a skin-resorptive effect, is characterized by a weak cumulative effect and does not it has sensitizing activity. Under the conditions of inhalation of the substance into the body of laboratory animals (rats), the threshold values of acute and chronic harmful effects of this pharmaceutical substance were at the level of 90 mg/m3 (in terms of the effect on the functional state of the nervous activity of rats) and 30 mg/m3, respectively (in terms of changes in behavioral indicators, weight and mass coefficient spleen, blood glucose, alanine aminotransferases and urea) accordingly.
 Conclusion. Based on the experimental results of the toxicological assessment, the authors have justified the standard of permissible content of the pharmaceutical substance ambroxol hydrochloride in the air of the working area at the level of 4.0 mg/m3, they also have established the hazard class of the substance according to GOST 12.1.007-76 (class 3, medium-hazard substances).
 Ethics. The Bioethics Commission of the State Enterprise "SPCH” has approved the use of laboratory animals for experimental purposes (Protocol No. 1 dated 03/04/2020). The treatment of animals was in accordance with the provisions of Directive 2010/63/EU of the European Parliament and of the Council of the European Union of September 22, 2010 on the protection of animals used for scientific purposes.

Development and validation of a method for the quantitative determination of metoprolol succinate in the air of the working area by high-performance liquid chromatography using mass spectra

Introduction. Metoprolol is a cardioselective blocker of β-adrenergic receptors. Drugs containing metoprolol have hypotensive, antianginal, antiarrhythmic effects. Moderately dangerous when taken orally, has a general toxic effect. Metoprolol is produced in two forms: in the form of salts of tartaric and succinic acids, the approximate safe level of exposure to which is 0.3 mg/m3. To ensure the safety of workers, it is necessary to carry out sanitary and hygienic air control. Methods for the quantitative analysis of metoprolol in the air of the working area, presented in the current scientific literature, allow monitoring only for metoprolol salts in the form of tartrate. 
 The aim of the study is to develop and validate an analytical method for the quantitative determination 
 of metoprolol succinate in the air of the working area by HPLC-MS. 
 Materials and methods. For the analysis, standard samples of metoprolol succinate and air samples taken at all stages of the life cycle of the production of the drug metoproolol were used. Chromatographic separation and detection were performed on an Agilent 1260 Infinity G6125B high performance liquid chromatograph (Agilent Technologies, USA) equipped with a column and sample thermostat, a degasser, a pump, an autosampler, and a G6125B mass selective detector. A Waters Xbridge® C18 3.5 µm column was used; 2.1×30 mm (Waters, Ireland). Primary data were processed using Open Lab CDS ChemStation Edition (Rev. C.01.07 SR3) software (Agilent Technologies, USA).
 Results. A method for the quantitative determination of metoprolol succinate in air samples by HPLC-MS has been developed and validated. During the validation of the developed methodology, it was found that the validation characteristics (specificity, linearity, accuracy and precision, correctness, reproducibility) are within the acceptance criteria. The analytical range of the technique was 0.1–10.0 µg/ml and allows the developed technique to be used to control the average shift MPCs in the air of the working area.
 Limitations. The results of the study of the air in the working area are applicable only to the production of the drug metoprolol in the form of tablets; the study of air during the synthesis and packaging of the active pharmaceutical substance was not carried out. 
 Conclusion. An analysis of air samples from the production of the drug metoprolol was carried out and the safety of working conditions was proved.

Development and application of a sustainable approach for the determination of 95 pharmaceutical substances and metabolites in urban wastewater by means of ultra-high-performance liquid-chromatography-tandem mass spectrometry

ABSTRACT In the last few years, the interest in pharmaceutical drugs and their metabolites as environmental pollutants is gaining growing importance. Regular monitoring and timely actions are decisive to implement appropriate water resource management strategies and to evaluate the efficiency of traditional or innovative wastewater treatment plants (WWTPs). This study describes the development and validation of an analytical procedure using 10 mL sample volume followed by direct-injection in ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 95 pharmaceutical drugs and 10 of their main metabolites in wastewater. Adequate sensitivity was recorded for all target analytes, with limits of detection below 5 ng/L for 60 out of 95 analytes and recoveries exceeding 80% for all the analytes under study. A total of 42 target analytes were detected in almost all sites, and limited differences were observed among several pharmaceutical drug arrays found at different sampling sites. In addition, an abatement yield higher than 50% was observed for only 12 of the 42 detected substances. The procedure, which combined direct injection and small sample volume collection, showed great potential and efficiency for the high-performance determination of pharmaceutical drugs in wastewater.

SYNTHESIS AND CHARACTERIZATION OF MOLECULAR IMPRINTED POLYMERS FOR PHENYLBUTAZONE EXTRACTION

Phenylbutazone is a pharmaceutical substance often added to rheumatic herbs. However, because of the complexity of the matrix caused by the presence of compounds in herbal medicines, the determination of phenylbutazone requires a time-consuming sample preparation process prior to analysis. This study was conducted to develop a specific sorbent that can be used to prepare phenylbutazone in herbal medicine. The performance of phenylbutazone Molecularly Imprinted Polymer (MIP) was evaluated using three distinct porogens (ethanol, methanol, and methanol-chloroform (1:1)) and two polymerization procedures (bulk and precipitation). According to the results of the polymer optimization, the polymer generated by precipitation in methanol-chloroform (1:1) has good sorbent characteristics. FTIR physical characterization revealed complete polymerization. The bulk procedure produces a more physically stable sorbent than the precipitation method does.  Keywords: MIP Performance Evaluation, Phenylbutazone Molecular Imprinted Polymer, Polymer Imprinting Factor

Effects of Pharmaceutical Substances with Obesogenic Activity on Male Reproductive Health.

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.

Structure Identification and Risk Assurance of Unknown Impurities in Pramipexole Oral Drug Formulation.

Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson's disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct.

Laccases as Effective Tools in the Removal of Pharmaceutical Products from Aquatic Systems.

This review aims to provide a comprehensive overview of the application of bacterial and fungal laccases for the removal of pharmaceuticals from the environment. Laccases were evaluated for their efficacy in degrading pharmaceutical substances across various categories, including analgesics, antibiotics, antiepileptics, antirheumatic drugs, cytostatics, hormones, anxiolytics, and sympatholytics. The capability of laccases to degrade or biotransform these drugs was found to be dependent on their structural characteristics. The formation of di-, oligo- and polymers of the parent compound has been observed using the laccase mediator system (LMS), which is advantageous in terms of their removal via commonly used processes in wastewater treatment plants (WWTPs). Notably, certain pharmaceuticals such as tetracycline antibiotics or estrogen hormones exhibited degradation or even mineralization when subjected to laccase treatment. Employing enzyme pretreatment mitigated the toxic effects of degradation products compared to the parent drug. However, when utilizing the LMS, careful mediator selection is essential to prevent potential increases in environment toxicity. Laccases demonstrate efficiency in pharmaceutical removal within WWTPs, operating efficiently under WWTP conditions without necessitating isolation.

A Survey of U.S. and Canadian Physicians’ Clinical Practices Related to Pharmacologic, Herbal, and Nutritional Substances Used to Increase Milk Production

Objectives:Physicians may be asked to prescribe, recommend, or discuss foods, herbs, and medications for low milk supply. It is unclear how factors such as education, experience, and regulations influence clinical practice. The objective was to document physicians’ clinical practice surrounding pharmacologic, nutritional, and herbal products for the management of low milk supply.Methods:Physicians from two Facebook groups completed an anonymous, online survey about their clinical use of pharmaceutical, supplemental, and nutritional substances perceived to increase milk production. The association between practice patterns and lactation medicine expertise or country for different perceived galactagogues was determined.Results:A total of 307 physicians completed the primary portion of the survey. There was no difference in the proportion of physicians in Canada or the United States (U.S.) who were defined as lactation medicine experts. Canadian physicians were more likely to prescribe metformin, levothyroxine, and domperidone for low milk supply compared with U.S.-based physicians. Canadians and experts were more likely than U.S.-based and nonexpert physicians, respectively, to include herbs in their practice. Patient request, personal and clinical experience, and lack of education, research, or access were frequently selected as reasons for or against using a specific substance.Conclusions:The U.S. Food and Drug Administration ban on domperidone affects low milk supply management in North America. Though Canadian physicians prescribed domperidone without limitations, U.S. physicians were less likely to incorporate it into clinical practice. Despite a lack of evidence, physicians in North America frequently used herbs and foods to increase milk production.

New Molecular Complexes of Glycyrrhizic Acid Monoammonium Salt (Glycyram) with Fluoroquinolone Antibiotics

Aims: The study aimed to search of new molecular complexes of licorice saponin with fluoroquinolone antibiotics and to explore their pharmaceutical potential. Background: Molecular complexation of triterpene glycosides with pharmaceutical substances reduces side effects and therapeutic doses, increases bioavailability and stability, and expands the spectrum of biological activity of drugs. Glycyrrhizic acid is the major triterpene glycoside of licorice. Molecular complexes of monoammonium salt of glycyrrhizic acid (glycyram, GC) with fluoroquinolone antibiotics have not been described. Objectives: This study is devoted to the preparation and analysis of molecular complexes of GC with fluoroquinolones, and investigation of their antimicrobial activity. Methods: Complexation was studied via FT-IR spectroscopy, UV-Vis spectroscopy and mass spectrometry methods. Results: Molecular complexes of GC with fluoroquinolone antibiotics, along with their benzylated derivatives, were obtained for the first time. Conclusion: The complexes composition was defined as 1:1. Intermolecular hydrogen bonds are formed during complexation. In addition, stability constants of 105 М-1 order were calculated. Some complexes are comparable in antimicrobial activity with individual antibiotics ciprofloxacin (CP) and moxifloxacin (Moc) or surpass them in relation to a number of bacteria. These molecular complexes could be potential low-dose drugs with antimicrobial activity.

Atomic absorption determination of copper and zinc in pharmaceutical preparations

The effect of Triton X-100 surface-active substance on the value of the analytical signal during the atomic absorption determination of copper and zinc was studied. It was shown that the maximum value of the analytical signal in the determination of analytes is achieved when Triton X-100 is used at a mass fraction of 5%. The sensitivity of the atomic absorption determination of copper increases by 1.74 times and that of zinc by 1.58 times. Sample preparation of pharmaceutical substances was carried out using ultrasound treatment. The most complete extraction of metals was achieved when the samples were treated with ultrasound for 25 minutes, and homogeneous solutions were obtained. The use of acetylacetonates of metals as standard samples of the composition increased the accuracy of copper and zinc determination due to the similarity of the calibration and analyzed solutions. The correctness of the result of the atomic absorption analysis was checked by the "injected-found out" method and by varying the weight of the sample. It was established that the systematic error is not significant. The limits of detection of copper (Cmin=0.002 g/ml, Ctheor=0.004 g/ml) and zinc (Cmin=0.003 g/ml, Ctheor=0.004 g/ml) were determined by the atomic absorption method, they are lower than those given in literature.

Natural Products and Derivatives Applied for Skin Care: An Updated Review

Abstract: In contemporary cosmetics, botanicals and natural extracts remain vital components and have been used in formulations since ancient times. However, natural and botanical products can still be highly effective in treating aging skin, even though they are becoming more technological and invasive. Many natural products are being elucidated through biochemical mechanisms of action, correlating with traditional uses of many plants for skin benefits. Different formulations of medicinal and pharmaceutical substances incorporate synthetic molecules and chemicals, which is the principal cause of dermal toxicity. Consumers' awareness about personal health and safety and the desire for safer cosmetics free of harmful chemicals have driven the cosmetics and personal care market toward natural ingredients. The commercialization of natural products derived from herbs and bees is possible. Our purpose is to present a comprehensive and critical review emphasizing the benefits of natural products for skin care, women's purchasing patterns, and updated information about natural products.

ИСПОЛЬЗОВАНИЕ УФ-СПЕКТРОФОТОМЕТРИИ В АНАЛИЗЕ И СТАНДАРТИЗАЦИИ СУБСТАНЦИИ 2-БЕНЗОИЛАМИНО-N-[4-(4,6-ДИМЕТИЛПИРИМИДИН-2-ИЛСУЛЬФАМОИЛ)-ФЕНИЛ]-БЕНЗАМИДА

Borderline neuropsychiatric disorders firmly hold a leading position in a large group of mental illnesses, among which neuroses occupy a significant place. The increasing number of patients with diseases associated with neuropsychiatric disorders makes the search and introduction of highly effective anxiolytics and antidepressants into medical practice increasingly important. In parallel with the search for medicinal substances with such pharmacological properties, it is necessary to resolve issues of standardization and quality control. One of these drugs may be a new synthetic derivative of ortho-benzoylaminobenzoic acid, which has antidepressant and anxiolytic effects. This compound was synthesized at the department of organic chemistry of the Pyatigorsk Medical and Pharmaceutical Institute under the leadership of professor Kodonidi I.P. Several biologically active compounds were synthesized - derivatives of o-benzoylaminobenzoic acid, one of which is 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl)-phenyl]-benzamide (laboratory code - PMFI-195) . Preliminary pharmacological studies of PMFI-195, carried out on the basis of the Federal State Budgetary Educational Institution of Higher Education of the Stavropol State Medical University of the Ministry of Health of Russia and the Federal State Budgetary Educational Institution of Higher Education of the North Caucasus Federal University, under the leadership of professor Manvelyan E.A., showed the promise of developing a drug based on the substance PMFI-195 for the treatment of such diseases such as depression, neuroses, psychopathy, neurosis-like and psycho-like states. Quality control and development of modern methods of pharmaceutical analysis is one of the basic stages of introducing pharmaceutical substances into production. This requires an in-depth study of physicochemical characteristics, as well as the selection and justification of methods of analysis and quality control of pharmaceuticals. substances. The results of the developed method for the qualitative determination by UV spectrophotometric method of a new quinosalinone derivative 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl)-phenyl]-benzamide, which has anxiolytic and antidepressant activity, are presented.

ПРИМЕНЕНИЕ СОРБЕНТА ДЛЯ ТВЕРДОФАЗНОЙ ЭКСТРАКЦИИ НА ОСНОВЕ ГИПРОМЕЛЛОЗЫ ДЛЯ КОЛИЧЕСТВЕННОГО ОПРЕДЕЛЕНИЯ КИСЛОТЫ САЛИЦИЛОВОЙ В КОМБИНИРОВАННЫХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТАХ

Introduction. In quality control of pharmaceutical formulations, there are methodological approaches based on the preliminary separation of sample components and approaches without preliminary separation. The use of solid-phase extraction (SPE) allows to separate analytes during sample preparation, with the separation selectivity determining the analysis selectivity as a whole. Currently, sorbents that provide selectivity in interaction with the analyte are of interest. Various derivatives of cellulose are used to obtain selective sorbents: ethylcellulose, hydroxypropylmethylcellulose (hypromellose), carboxymethylcellulose, etc. On the pharmaceutical market of the Russian Federation, there are pharmaceutical formulations with the active pharmaceutical substance salicylic acid. The use of selective SPE for analysis is a promising direction of research in drug quality control. Aim. Evaluation of the metrological characteristics of benzocaine quantitation by UV-spectrophotometry in certain pharmaceutical formulations using hypromellose sorbent for solid-phase extraction. Material and methods. The sorbent using a method developed by us was obtained. Salicylic acid (FS.2.1.0634, Russia State Pharmacopoeia XV ed.) to form active binding sites in sorbent structure was applied. The sorbent structure is polycyanoacrylate matrix with hypromellose fragments, the surface area is 255.50 m2/g, pore volume is 0.1433 cm3, pore diameter is 5.32 nm. The sorption capacity of hypromellose sorbent for benzocaine was 12.2 ± 0.8 μg/g. The SPE technique is proposed. SPE includes the stages: conditioning, sample addition and step-by-step elution with purified water and sodium hydroxide solution 0.1 mol/L. The spectrophotometer SF-56 was used to measure the absorbance at an analytical wavelength of 286 nm. To evaluate the selectivity (specificity) of sample preparation during chromatographic (SPE) separation of pharmaceutical formulations, absorption spectra of eluates in the wavelength range of 200-400 nm were scanned. The salicylic acid identification in the eluate was carried out based on absorption peaks at 228 and 298 nm.The salicylic acid calibration curve in the range of 1-20 μg/ml. To determination the metrological characteristics of salicylic acid quantitation method, 16 parallel determinations of samples of each pharmaceutical formulation were made. Statistical processing of the experimental results and determination of the metrological characteristics evaluation of analytical technique were carried out in accordance with general pharmacopoeial monograph (OFS.1.1.0013 "Statistical processing of results of physical, physicochemical, and chemical tests"). Results. When realizing the salicylic acid quantitation technique for measuring absorbance, it is advisable to use only the first portions of eluate (a solution of sodium hydroxide) in a volume of 5-10 ml were obtained. The relative error in determining the average content of salicylic acid in the analyzed preparations ranged from 1.18 to 1.44% for methods with solid-phase extraction (SPE) and 1.86-2.62% in its absence. It has been shown that there is a statistically significant difference in reproducibility for all preparations, as indicated by F-criteria values ranging from 7.81 to 13.5, exceeding their tabulated values. For the method without solid-phase extraction (SPE), there was an overestimation of the salicylic acid content in all cases, increasing the systematic error on average by 87.5%. Conclusion. The possibility of using a selective hypromellose sorbent for sample preparation for salicylic acid quantitation determination in pharmaceutical formulations has been showed. The use of sorbent for analysis provides to systematic error decrement of salicylic acid quantitation by an average of 87.5%.

Methodological and regulatory aspects of pharmaceutical development of biological products

The aim of the work was to conduct an analysis of the current state and current trends in the approval of drugs, as well as some aspects of the methodology for their development based on biological molecules and registration.Materials and methods. The material for the analysis was taken from the abstract databases of PubMed, Google Scholar and e-library.ru. The search was carried out using publications for the period from 2008 to 2023, the keywords were as follows: “biologicals”, “new drug approval”, “drug authorization”, “drug development”, “biosimilar”, taking into account various spellings.Results. Over the past 15 years, scientists have been observing revolutionary trends and processes in the field of the drug development, especially biopharmaceuticals. Significant advances have been made in gene, immune and cell therapies, resulting in the approval of such drugs more than doubling over the past ten years. The development of biological drugs includes the identification and testing of molecular targets and requires a deep understanding of the structure and functioning of the polypeptides involved in the development of the effect. The features of these active pharmaceutical substances are a high molecular weight, a complex three-dimensional structure and a high immunogenic potential. Preclinical and clinical studies of biologics have unique challenges. Selecting appropriate animal species, understanding the immunogenicity, and assessing pharmacodynamics and toxicological properties require a multilevel, detailed approach. The article discusses the regulatory framework under which these drugs are registered, summarizing the guidelines provided by international organizations such as the International Council for Harmonization and various national agencies.Conclusion. The analysis highlights the current advances and prospects in the development of biologics, highlighting their key role in future transformations in the treatment of rare diseases and oncology, approaching the era of personalized medicine. Monitoring the development directions and technological approaches, as well as the commitment to global methodological and regulatory aspects can become a catalyst in the development of the Russian pharmacology.

Determination of the composition of pharmaceutical substances used in drugs with antiarrhythmic activity

Cardiac arrhythmias are the most common pathologies of the cardiovascular system. Allapinin® and Allaforte® from “Pharmcenter VILAR” are effective IC-class antiarrhythmic agents. The main component of these drugs is a pharmaceutical substance with INN: lappaconitine hydrobromide, which in addition to lappaconitine hydrobromide itself, contains impurities of other diterpene alkaloids. This work is devoted to a detailed analysis of the alkaloid composition of a new pharmaceutical substance isolated from roots and rhizomes, as well as from the aerial part of plants of the genus Aconite (monkshood, wolfsbane) of the Ranunculaceae family (buttercups) using chromato-mass spectrometry and NMR spectroscopy. In addition, an assessment was made of the quantitative ratios of alkaloids in several samples of pharmaceutical substances isolated from different batches of medicinal plant raw materials.

Presumptive injection-site sarcoma in a white tiger (Panthera tigris tigris): A case report

A 6-year-old female White Tiger (Panthera Tigris Tigris) was presented with a history of a recurrent ulcerating mass on the right lumbar wall which initially, was removed by surgery one year before presentation.  Cytological and histological findings were consistent with a cutaneous injection site sarcomas. Immunohistochemistry results revealed that the neoplastic cells were strongly positive for vimentin and weakly positive for alpha-smooth muscle actin (SMA), but negative for Cytokeratin AE1/AE3, s100, and Desmin. Positive staining for vimentin and SMA is consistent with myofibroblast reactivity and reflects a continuous inflammatory response seen in feline injection-site sarcomas.  Feline injection-site sarcomas are the most serious adverse effect following injection of the vaccine or some other pharmaceutical substances and should be considered in the differential diagnosis of skin swelling in injection sites in the Felidae family. Limited data are available for these tumors in animals outside of domesticated cats. To the best of our knowledge, there exists no available published information on the injection-site sarcoma in tigers. Similar to domestic felids, this case highlights the importance of considerations and management options in vaccination schedules for the reduction of sarcoma risk in wild felids.