Drug development & registration最新文献

{"title":"Recommendations for Validation of Automated Viable Cell Counting Methods (Review)","authors":"M. Vodyakova, N. S. Pokrovsky, E. Melnikova, Vadim A. Merkulov, М. А. Водякова, Н. С. Покровский, Е. В. Мельникова, В. А. Меркулов","doi":"10.33380/2305-2066-2023-12-4-1424","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1424","url":null,"abstract":"Introduction. The quality of viable cell-based products (such as biomedical cell products and advanced therapy medicinal products) must be maintained during the full production cycle to ensure their safety and efficacy for patients. The minimum required number of viable cells is one of the quality control criteria in the final product release specifications. This study looks into the process of validation of automated viable cell counting methods.Text. The study reviewed the latest data on specific validation characteristics for automated cell counters as compared to manual counting methods. We identified the main problems with the validation methods. Based on the review of scientific and regulatory literature, we identified the key validation parameters, methods of their evaluation and measurement, and reporting of results. We described the validation algorithm for an automated cell counter, including such steps as the selection of reference standards, selection of the number of experimental points, experimental design, mathematical evaluation of the obtained results, and determination of the acceptance criteria.Conclusion. Based on the data reviewed, the authors developed recommendations for the validation of automated viable cell counting procedures.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"50 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139264597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the Effect of Matrix-forming Polymers on the Release Rate of Sodium 4,4'-(propanediamido)dibenzoate from Tablets","authors":"2305-2066-2023-12-4-1579УДК, Ю. М. Коцур, Е. В. Флисюк, К. О. Сидоров, И. А. Титович, И. А. Наркевич, Yu. M. Kotsur, E. V. Flisyuk, K. O. Sidorov, Irina A.Titovich, Igor A. Narkevich","doi":"10.33380/2305-2066-2023-12-4-1579","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1579","url":null,"abstract":"Introduction. Wet granulation technology is a process of directed particle aggregation of powder materials to obtain required properties of tablet masses and, as a consequence, to achieve satisfactory characteristics of tablets. In this addition, as a result of wet granulation technology, if special excipients are used, it becomes possible to control the rate and kinetics of release of active pharmaceutical substances from tablets to achieve the desired therapeutic effect.Aim. To study the effect of matrix-forming components included in the composition of mixtures for granulation on the rate of release of sodium 4,4'-(propanediamido)dibenzoate from tablets.Materials and methods. The original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of excipients, which included polymers used for prolonged-release dosage forms, lubricant – sodium stearyl fumarate, as well as pore-forming agents – PVP and MCC, were the objects of the study. The key parameters of tablets and dissolution kinetics were studied in accordance with the requirements of State Pharmacopoeia of the Russian Federation XIV edition and Pharmacopeia of the Eurasian Economic Union.Result and discussion. Prolonged release was achieved for all tablets, but more than 90 % of the substance was released after 12 hours in tablets containing ethylcellulose as a matrix-forming polymer. The release of APS from tablets of this formulation was the most prolonged.Сonclusion. The effect of matrix-forming components included in the composition of mixtures for granulation on the rate of release of 4,4'-(propanediamido)sodium dibenzoate from tablets has been studied. The most uniform and complete release of ASF from tablets in which the matrix-forming polymer is ethylcellulose in the amount of 27.7 %.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139264978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiarrhythmic Activity of Amino Acids Containing Nibentan Derivatives in Case of Symptoms of Occlusive and Reperfusion Arrhythmias","authors":"S. M. Napalkova, O. V. Buyuclinskaya","doi":"10.33380/2305-2066-2023-12-3-212-217","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-212-217","url":null,"abstract":"Introduction. Pharmacotherapy of cardiac arrhythmias is one of the urgent problems of modern medicine. The presence of serious side effects, in particular proarrhythmic action, limits the use of known antiarrhythmics in clinical practice. One way to reduce the toxicity of pharmacological agents is to use them as complex compounds with amino acids.Aim. Studying the effect of nibentan derivatives containing magnesium salt of L-aspartic acid and glycine as anions on the course of early occlusive and reperfusion arrhythmias.Materials and methods. Aminоacid derivatives of nibentan have been studied in models of occlusive and reperfusion arrhythmias in rats. The activity of the drugs was assessed by the incidence of ventricular extrasystoles (VEC), ventricular tachycardia (VT), ventricular fibrillation (VF), by the latent period and duration of arrhythmias, the average duration of VT, and by the number of VEC per 1 animal.Results and discussion. Nibentan derivatives in models of early occlusive and reperfusion arrhythmias were not inferior in antiarrhythmic activity to lidocaine and nibentan in their ability to prevent cardiac arrhythmias. The nibentan derivative containing the magnesium salt of L-aspartic acid (compound LHT-53-91) in the model of occlusive arrhythmias at a dose of 2 % LD50 completely prevented cardiac arrhythmias in experimental animals. A nibentan derivative containing glycine (compound LHT-20-92) at a dose of 1 % LD50 significantly reduced the number of cases of PVCs, prevented the occurrence of ventricular tachycardia and ventricular fibrillation in 100 % of cases. In the model of reperfusion arrhythmias, LHT-53-91 at a dose of 1 % LD50 prevented the development of ventricular fibrillation and paroxysms of ventricular tachycardia and reduced the risk of developing ventricular extrasystole (p < 0.05). Increasing the dose to 2 % LD50 led to an increase in the activity of the substance, which was expressed in the prevention of cardiac arrhythmias in 100 % of the animals. LHT-20-92 at a dose of 1 % LD50 in this model of cardiac arrhythmias statistically significantly reduced the occurrence of VES and VT paroxysms and completely prevented the occurrence of VF (p < 0.05).Conclusion. The inclusion of nibenthan amino acids in the structure, which shielded genotic grouping and reduced potential teratogenicity and mutagenicity, had not led to a reduction in the antiarrhythmic and antifibril-torn activity on the studied models of rhythm disorders.","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88313377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of Myocardial Structure after Developed Fibrous Degeneration Under the Use of Allogenic Biomaterial","authors":"A. Lebedeva, S. Afanasiev, E. M. Gareev, D. Kondratieva, L. A. Musina, S. V. Popov, A. Prusakov, A. Yashin, V. S. Ponamarev, V. D. Radnatarov","doi":"10.33380/2305-2066-2023-12-3-202-211","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-202-211","url":null,"abstract":"Introduction. The question of the possibility of recovery of postischemic myocardium remains relevant.Aim. The aim of the study was to study the effect of dispersed decellularized allogeneic extracellular matrix (allogeneic biomaterial, DAB) on the developed fibrous degeneration of the myocardium, as well as to reveal the possible mechanisms of cellular regeneration.Materials and methods. The muscular wall of the heart of rats was subjected to cryodestruction. After 45 days, the rats of the main group were intramyocardially injected with a suspension of allogeneic biomaterialinto the area of the affected myocardium, and the rats of the control group were injected with saline.Results and discussions. In the experimental group, there was a regression of the formed fibrous connective tissue, chemoattraction of progenitor cells, their differentiation and integration into the myocardium. The thickness of the muscular part of the wall of the left ventricle was three orders of magnitude higher than in the control group.Conclusion. Analysis of the results of the study indicates that the heart in adult mammals has a powerful regenerative reserve. It is likely that, based on the use of DAB, a protocol can be developed that allows the restoration of the heart muscle even in conditions of already developed fibrous degeneration.","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89801452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Double-blind Randomized Comparative Phase I Study to Assess Biosimilarity and Immunogenicity of \"Trastuzumab\" (LLC \"Mabscale\", Russia) and Herceptin® (F. Hoffmann-La Roche Ltd., Switzerland) in Healthy Volunteers","authors":"М. А. Колганова, Е. Е. Бекетов, В. В. Писарев, А. В. Иванов, С. В. Васильев, И. Е. Шохин, M. A. Kolganova, Evgeny E. Beketov, Vladimir V. Pisarev, Andrei V. Ivanov, Sergey V. Vasiliev, I. E. Shokhin","doi":"10.33380/2305-2066-2023-12-3-240-249","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-240-249","url":null,"abstract":"Introduction. Trastuzumab is the first drug based on the monoclonal antibodies’ technology targeted to the neu oncogene expression product discovered in the middle 80-s – human epidermal growth receptor, HER2. After being approved trastuzumab had become the drug of choice for combine therapy of metastatic breast cancer (BC). This therapy had also allowed to improve patients’ 5-year survival rate dramatically, almost up to 90 % in some cases. Despite the fact that more than 10 biosimilars of trastuzumab are now in the pipeline around the world, including Russia, the development and registration of trastuzumab biosimilars still remain relevant.Aim. Aim of the study was to conduct the analytical part of the double-blind randomized comparative clinical trial for trastuzumab pharmacokinetics and safety assessment in healthy volunteers with subsequent biosimilarity evaluation of \"Trastuzumab\" (LLC \"Mabscale\", Russia) and Herceptin® (F. Hoffmann-La Roche Ltd., Switzerland).Materials and methods. 92 healthy volunteers, who fulfilled the inclusion/exclusion criteria, were enrolled to the study. Trastuzumab quantitation and anti-trastuzumab antibodies detection was performed using ELISA method with photometric detection. To support the clinical trial two different independent bioanalytical methods were validated.Results and discussion. Trastuzumab quantitation method in human blood serum was validated for selectivity, calibration curve and regression model, sensitivity (LLOQ), accuracy and precision, MRD, dilution linearity and stability. The method for anti-trastuzumab antibodies detection, that was previously described by the authors, was validated for cut-point, selectivity, sensitivity, prozone effect, drug tolerance, precision and stability (short-term and long-term). The validated methods were successfully applied to the study samples assay to perform the analytical part of the comparative study for trastuzumab pharmacokinetics and immunogenicity assessment. The obtained drug concentrations were used for PK-parameters and confidence interval calculations to estimate the biosimilarity of test and reference drug.Conclusion. The study results showed that test and reference drug are biosimilar, and moreover immunogenicity assessment showed no anti-trastuzumab antibodies in any samples of healthy volunteers.","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88713511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Antistaphylococcal Activity of the Pyrimidine Derivative","authors":"A. Tsibizova, A. Yasenyavskaya, I. Tyurenkov, A. Ozerov, O. A. Baskina, M. Samotrueva","doi":"10.33380/2305-2066-2023-12-3-190-194","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-190-194","url":null,"abstract":"Introduction. The development of safe and effective drugs with antimicrobial activity is currently a priority task of modern pharmacology. The need to obtain new antimicrobial agents is associated with the presence of problems, the main of which is the development of polyresistance of the pathogenic pathogen to existing antibacterial drugs. Of particular interest as a basis for the creation of drugs are pyrimidine compounds, which have a wide range of pharmacological effects, namely psycho- and neurotropic, metabolic, anti-inflammatory, antioxidant, antitumor, immunotropic, etc. Also, the advantage of pyrimidines is the simplicity of the synthesis of new compounds based on them by attaching various functional groups to the heterocycle.Aim. Evaluation of antistaphylococcal activity of a new pyrimidine derivative in vitro and in vivo.Materials and methods. Antistaphylococcal activity of pyrimidine derivative 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazolin-4(3H)-oh (VMA-13-13) was studied in vitro using a test culture of a strain of Staphylococcus aureus (Staphylococcus aureus) using the method of serial dilutions. St. aureus was isolated from the sputum of patients treated in inpatient conditions of GBUZ JSC \"City Clinical Hospital No. 3 named after S. M. Kirov\" (Astrakhan). The minimum suppressive concentration (MPC) of 2-Methyl-3-(2-phenyl-2-oxoethyl) was determined in the studyquinazoline-4(3H)-oh in relation to St. aureus. In vivo, antimicrobial activity studies were conducted on a model of generalized infection caused by intraperitoneal administration of 1 ml of St. aureus drug containing 1 × 108 CFU/ml to mice. Laboratory animals were divided into several groups: control I – animals receiving an equivalent volume of water for injection; control II – animals infected with St. aureus; experimental groups – receiving the comparison drug ceftriaxone (Biosynthesis JSC, Russia) at an average therapeutic dose of 50 mg/kg; and mice treated with a pyrimidine derivative mixed with water for injection, at a dose of 1/10 of the molecular weight of 27 mg/kg, starting from the day of infection for 7 days. The study evaluated the effect of pyrimidine derivative on animal survival. At the end of the experiment, the index of contamination of blood, spleen, liver and lungs was calculated.Results and discussion. In the study, it was found that the MPC of ceftriaxone, in which this drug had bacteriostatic activity against the St. aureus strain, corresponded to 1 mcg/ml, whereas for the pyrimidine derivative VMA-13-13, the MPC was 16 mcg/ml; the bactericidal effect of the comparison drug was caused at a minimum concentration of 32 mcg/ml, and the substance under study is in a concentration of 64 micrograms/ml. The formation of generalized staphylococcal infection led to a decrease in the survival rate of animals in the untreated control group up to 30 %; with the introduction of ceftriaxone and pyrimidine derivative – up to 80 % compared with the intact control. When ","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76703433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of Elemental Composition of Herbal Medicinal Raw Materials of Voronezh Region","authors":"N. Dyakova","doi":"10.33380/2305-2066-2023-12-3-195-201","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-195-201","url":null,"abstract":"Introduction. The available information on the elemental composition of medicinal plant raw materials of the Voronezh region showed that studies are carried out mainly on several elements, which does not allow determining the complete mineral complex of medicinal plants and describing the specifics of the accumulation of individual elements in them.Aim. The purpose of the study is to study the macro- and microelement composition of medicinal plant raw materials of the Voronezh region on the example of a protected area.Materials and methods. Pharmacopoeic types of medicinal vegetal raw materials were used as subjects of investigation: nettle leaves dioecious (Urtica dioica L.), plantain leaves large (Plantago major L.), common pajma flowers (Tanacetum vulgare L.), heart-shaped linden flowers (Tilia cordata Mill.), herb of five-lobed dumplings (Leonurus quinquelobatus Gilib.), grass of bitter wormwood (Artemisia absinthium L.), common millennium grass (Achillea millefolium L.), bird mountain grass (Polygonum aviculare L.), roots of the common bladder (Arctium lappa L.), roots of the dandelion drug (Taraxacum officinale F.H. Wigg). Raw material harvesting was carried out in accordance with pharmacopoeic rules in natural thickets in the Voronezh State Natural Biosphere Reserve named after V. M. Peskov in the Ramonsky district. The microelement composition of the samples was studied mass-spectroscopically on an ELAN DRC device (PerkinElmer Instruments, USA) after acid-microwave decomposition.Results and discussion. In each plant sample, 59 elements were quantified. The content of the total elemental complex in the studied types of LRs varies from 1.91 to 7.68 % in terms of dry raw materials. The studied raw materials accumulate macroelements to the greatest extent (more than 84 %). Essential trace elements accumulate most in dioecious nettle leaves (more than 9 mg/g). Of the essential trace elements, silicon and iron accumulate most of all the studied raw materials. Content of regulated toxic trace elements does not exceed requirements of pharmacopoeia.Conclusion. The results of the study showed a complex macro- and microelement composition of the studied medicinal vegetal raw materials, which can be used in the medical and pharmaceutical practice of creating phytopreparations and biologically active additives for correcting physiological norms of the content of elements in the human body. The most quantitatively rich elemental composition is noted for the grass of five-lobed dumplings, nettle leaves of dioecious and large plantain (more than 50 mg/g).  ","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"123 18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72618183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level","authors":"A. N. Arevefa, A. Dorotenko, S. Noskov, I. Makarenko, R. V. Drai, T. N. Komarov, O. A. Archakova, N. S. Bagaeva, I. E. Shokhin","doi":"10.33380/2305-2066-2023-12-3-218-227","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-218-227","url":null,"abstract":"Introduction. Citicoline is an endogenous nucleoside consisting of cytidine and choline linked by a diphosphate bridge that is involved in the synthesis of membrane phospholipids. Drugs containing citicoline have neuroprotective and neurometabolic effects and are used for the treatment of a wide range of neurological disorders. In its turn, bioequivalence study is a pathway to register a generic citicoline drug in Russian Federation.Aim. The aim of the study was to investigate the comparative pharmacokinetics (PK) and bioequivalence of two citicoline-containing drugs GP30121 and Ceraxon® in healthy male volunteers when taken on an empty stomach.Materials and methods. We evaluated the pharmacokinetics of citicoline-containing drugs corrected for endogenous analyte (uridine) level using an adaptive design. We determined uridine concentration by high-performance liquid chromatography with mass spectrometric detection. We used R Project software, version 3.6.3. for performing statistical analysis for the study.Results and discussion. GP30121 and Ceraxon® exhibited similar PK profiles. It was shown that the values of 94.12 % confidence interval (CI) at α = 0.0294 for the geometric mean ratios for the primary PK parameters of the main metabolite of the active ingredient of the investigated drugs were fully contained within the predefined equivalence limits of 80.00–125.00 %.Conclusion. The study demonstrates bioequivalence of GP30121 and Ceraxon® proving the approach with the correction for endogenous analyte could be considered in studies of other drugs.","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87716379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological Approaches to Risk Management of Advanced Therapy Medicinal Products","authors":"A. Taube, N. Y. Velts","doi":"10.33380/2305-2066-2023-12-3-250-259","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-250-259","url":null,"abstract":"Introduction. Advanced therapy medicinal products (ATMPs) rely on recent advances in medical science, but alongside with potential benefits they may also bring safety concerns for patients. The inherent complexity of the ATMP production and use calls for special approaches to risk management throughout their lifecycle, from obtaining the raw materials to administration to the patient.Aim. The aim of the present study was to develop approaches to risk management for ATMPs, using the example of CAR T-cell therapy.Materials and methods. The study analysed the relevant regulatory frameworks currently in force in the European Union and the United States of America, namely the regulations and guidelines adopted by the Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration and the Committee for Medicinal Products for Human Use of the European Medicines Agency.Results and discussion. The paper provides a classification of patient risks, which was developed based on the European risk-based approach. It formulates the principles of risk management for each of the risks, depending on the stage of the product life cycle. Each type of risk was considered separately. The following risk minimization strategies were determined: compliance with the good practices, ensuring the necessary qualifications or expertise of all parties involved in the product life cycle. The main element of risk control is the detailed description of the medicinal product use in the summary of product characteristics and patient information leaflet.Conclusion. The study identified the main stages at which ATMP risks may occur, and each type of risk was considered separately. The following requirements should be put in place in order to manage the ATMP risks: requirements for distributors on how to perform the product transportation and storage and to keep records for the marketing authorisation holder; requirements for healthcare facilities on how to perform the product storage, its preparation for use, advising and informing the patients on the treatment risks, symptoms of adverse events, preparatory and follow-up medical procedures, and on how to keep records for the marketing authorisation holder; requirements for the qualifications of healthcare professionals who are in charge of the product storage, its preparation for use, treatment procedures, advising and informing the patients on the treatment risks, symptoms of adverse events, and follow-up medical procedures. The data obtained will be used in the preparation of recommendations for ATMP developers.","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75622584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Favipiravir in Human Blood Plasma by HPLC-MS/MS","authors":"T. N. Komarov, P. A. Karpova, O. A. Archakova, D. S. Shchelgacheva, P. K. Karnakova, N. S. Bagaeva, K. Zaslavskaya, P. A. Bely, I. Shohin","doi":"10.33380/2305-2066-2023-12-3-229-239","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-229-239","url":null,"abstract":"Introduction. Favipiravir is one of the most well-known broad-spectrum drugs against many RNA viruses, including the severe acute respiratory syndrome virus 2 [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]. Due to its structure, favipiravir is embedded in the RNA of the virus and blocks its further replication in the cell of the human body. Favipiravir is also included in the list of vital and essential medicines, which confirms the importance for Russian healthcare of this drug in the fight against common RNA viruses. We have already published bioanalytical methods for determining favipiravir in human blood plasma by high-performance liquid chromatography with an ultraviolet detector (HPLC–UV) in order to study the pharmacokinetics of favipiravir with parenteral administration (the analytical range of the technique was 0.25–200.00 µg/ ml for the dosage of favipiravir 400 mg in 1 vial of lyophilizate for the preparation of concentrate for the preparation of solution for infusions) and by HPLC with tandem mass-selective detection (HPLC-MS/MS) in order to study the pharmacokinetics of β-D-N4-hydroxycytidine and favipiravir in their joint determination in blood plasma with oral administration (the analytical range of the technique was 250.00–20000.00 ng/ml for the dosage of favipiravir 400 mg in 1 tablet). The expectation of low favipiravir’s concentrations (the dosage of favipiravir in the drugs in question is 200 mg in 1 tablet in this study) and, in this regard, the expansion of the range by reducing the value of the lower limit of quantitative determination (LLOQ) used in this study necessitates the development of another method. Therefore, this study is given the development and validation of a method for determining favipiravir in human blood plasma by HPLC-MS/MS with an analytical range of 50.00–15000.00 ng/ml.Aim. The aim of this study is to develop a method for quantitative determination of favipiravir in human blood plasma by HPLC-MS/MS for further for further researches of pharmacokinetics and bioequivalence of drugs.Materials and methods. In the process of sample preparation, a method of proteins precipitation with methanol was used. A solution labeled with stable isotopes of favipiravir-13C3 was used as an internal standard, the mobile phase was a 0.1 % solution of formic acid in water (eluent A) and methanol (eluent B). Chromatographic column – Phenomenex Kinetex C18, 100×3.0 mm. The determination of favipiravir in human blood plasma was carried out by HPLC using a tandem mass spectrometric detector with a triple quadrupole. The analytical range for favipiravir is 50.00– 15000.00 ng/ml in human blood plasma.Results and discussion. This method was validated by selectivity, calibration curve, accuracy, precision, matrix effect, spike recovery, carry-over effect, the lower limit of quantification and stability.Conclusion. A method of quantitative favipiravir’s determination in human blood plasma by HPLC-MS/MS with a confir","PeriodicalId":11259,"journal":{"name":"Drug development &amp; registration","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83043909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}