Pub Date : 2022-02-28DOI: 10.30895/1991-2919-2022-12-1-79-89
V. Kosenko, R. Yagudina, O. A. Lednev, V. Serpik
The available range of medicinal products is growing every year.The aim of the study was to analyse the range of medicines authorised in the Russian Federation.Materials and methods: the analysis covered the data presented in the State Register of Medicines (as of June 2021) and the current regulations specifying the range of medicines.Results: this article presents the results of analysis of medicines authorised in the Russian Federation, in terms of the following parameters: international non-proprietary names, trade names, groups according to the Anatomical Therapeutic Chemical Classification System, dosage forms, routes of administration, primary and secondary packaging, storage conditions, and shelf life. The analysis demonstrated that there are over 19 thousand medicines authorised in the Russian Federation, most of which are produced in Russia. The largest groups of medicines are antimicrobial products for systemic use, medicines for the treatment of nervous system and cardiovascular system disorders. The most common dosage form is tablets, and the most common primary packaging is vials. The most frequent storage temperature requirements are 15–25 and 2–8 °C. About half of all medicines have the shelf life of 3 years.Conclusions: the data presented in this article can be used for unification of approaches to maintaining the State Register of Medicines, elaboration of reference books, and will be useful for medicine developers and manufacturers when planning and preparing regulatory submissions.
{"title":"Analysis of the Medicinal Products for Human Use Authorised in the Russian Federation","authors":"V. Kosenko, R. Yagudina, O. A. Lednev, V. Serpik","doi":"10.30895/1991-2919-2022-12-1-79-89","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-79-89","url":null,"abstract":"The available range of medicinal products is growing every year.The aim of the study was to analyse the range of medicines authorised in the Russian Federation.Materials and methods: the analysis covered the data presented in the State Register of Medicines (as of June 2021) and the current regulations specifying the range of medicines.Results: this article presents the results of analysis of medicines authorised in the Russian Federation, in terms of the following parameters: international non-proprietary names, trade names, groups according to the Anatomical Therapeutic Chemical Classification System, dosage forms, routes of administration, primary and secondary packaging, storage conditions, and shelf life. The analysis demonstrated that there are over 19 thousand medicines authorised in the Russian Federation, most of which are produced in Russia. The largest groups of medicines are antimicrobial products for systemic use, medicines for the treatment of nervous system and cardiovascular system disorders. The most common dosage form is tablets, and the most common primary packaging is vials. The most frequent storage temperature requirements are 15–25 and 2–8 °C. About half of all medicines have the shelf life of 3 years.Conclusions: the data presented in this article can be used for unification of approaches to maintaining the State Register of Medicines, elaboration of reference books, and will be useful for medicine developers and manufacturers when planning and preparing regulatory submissions.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82360368","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}
Pub Date : 2022-02-21DOI: 10.30895/1991-2919-2022-12-1-24-40
N. E. Kuz’mina, S. Moiseev, E. Y. Severinova, A. I. Luttseva
Diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) is a molecular transport method in analytical chemistry, based on experimental recording of the molecules’ translational mobility at thermodinamic equilibrium in a solution. The translational mobility is characterised quantitatively by a self-diffusion coefficient. The aim of the study was to summarise the main trends in application of DOSY for the analysis of natural and modified natural polysaccharides used in pharmaceuticals and pharmaceutical biotechnology. The review shows that this method is an effective instrument for monitoring fractionation during isolation of polysaccharides from a natural mixture, for estimating their average molecular weight and molecular weight distribution, and for studying the formation of supramolecular systems based on polysaccharides. The paper describes main issues of the precise measurement of polysaccharide macromolecules self-diffusion coefficients and provides the correction factors to compensate for errors caused by fluctuations in temperature and viscosity of solutions. The observed scatter of self-diffusion coefficients of narrowly dispersed polymer macromolecules nuclei is explained using the polyphase concept. The paper illustrates ways of describing translational mobility of a polyphase polymer macromolecule as a whole. The authors summarise values of the gradient pulse sequence parameters used in quantitative measurements of self-diffusion coefficients of linear, low-branched, and branched polysaccharides.
{"title":"Diffusion-Ordered NMR Spectroscopy Application for Analysis of Polysaccharides","authors":"N. E. Kuz’mina, S. Moiseev, E. Y. Severinova, A. I. Luttseva","doi":"10.30895/1991-2919-2022-12-1-24-40","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-24-40","url":null,"abstract":"Diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) is a molecular transport method in analytical chemistry, based on experimental recording of the molecules’ translational mobility at thermodinamic equilibrium in a solution. The translational mobility is characterised quantitatively by a self-diffusion coefficient. The aim of the study was to summarise the main trends in application of DOSY for the analysis of natural and modified natural polysaccharides used in pharmaceuticals and pharmaceutical biotechnology. The review shows that this method is an effective instrument for monitoring fractionation during isolation of polysaccharides from a natural mixture, for estimating their average molecular weight and molecular weight distribution, and for studying the formation of supramolecular systems based on polysaccharides. The paper describes main issues of the precise measurement of polysaccharide macromolecules self-diffusion coefficients and provides the correction factors to compensate for errors caused by fluctuations in temperature and viscosity of solutions. The observed scatter of self-diffusion coefficients of narrowly dispersed polymer macromolecules nuclei is explained using the polyphase concept. The paper illustrates ways of describing translational mobility of a polyphase polymer macromolecule as a whole. The authors summarise values of the gradient pulse sequence parameters used in quantitative measurements of self-diffusion coefficients of linear, low-branched, and branched polysaccharides. ","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80471841","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}
Pub Date : 2022-02-21DOI: 10.30895/1991-2919-2022-12-1-56-64
V. I. Toporkova, A. O. Ponkratova, A. K. Whaley, V. Luzhanin, M. U. Goncharov
Plants of the Corydalis (Papaveraceae) genus are widely used in oriental medicine and are known for their particularly rich content of biologically active substances. One of the species encountered in Russia, the large-flowered corydalis (Corydalis bracteata (Steph. ex Willd.) Pers.), is widespread in Western and Eastern Siberia, but none the less its chemical composition has not been properly studied yet.The aim of the study was to perform phytochemical analysis of Corydalis bracteata herb through isolation of the main secondary metabolites and elucidation of their structure, using modern chromatographic methods of analysis and NMR spectroscopy.Materials and methods: the analysis was performed for dried aerial parts of C. bracteata. The isolation of individual compounds was performed using open-column chromatography and glass columns packed with sorbents with different selectivity characteristics— Dianion® HP-20 (Supelco) and Sephadex® LH-20 (GE Healthcare)—as well as preparative-scale chromatography with a Kromasil® C18 column and detection at 235 nm. Water and acetonitrile mixed in the ratios 5:95–50:50 v/v with the addition of 0.1% trifluoroacetic acid were used as the eluents. The analysis of fractions before pooling was performed by high-performance thin-layer chromatography with Silica gel 60 F254 plates (Merck). The analysis of the individual compound solutions was performed by HPLC using a Prominence LC-20 (Shimadzu) instrument, a SUPELCOSIL™ LC-18 column, and detection at 235 nm. The structures of the isolated individual compounds were elucidated by one- and two-dimensional NMR spectroscopy using a Bruker Avance III 400 MHz NMR spectrometer.Results: four individual compounds from the С. bracteata aerial parts were isolated and analysed: an isoquinoline alkaloid— coptisine (1) and three flavonoids—rutin (2), quercetin-3-O-β-D-glucopyranoside (3), and kaempferol-3-O-β-D-glucopyranoside (4).Conclusions: as a result of the phytochemical analysis of the С. bracteata aerial parts, compounds of both alkaloid and flavonoid nature were isolated for the first time, and their structures were elucidated using NMR spectroscopy. С. bracteata should be considered as a promising potential source of biologically active substances.
紫堇属植物在东方医学中被广泛使用，并以其特别丰富的生物活性物质含量而闻名。在俄罗斯遇到的一种，花大的紫堇(corydalis bracteata)。Willd交货)。)，广泛分布于西伯利亚西部和东部，但其化学成分尚未得到适当的研究。本研究采用现代色谱分析和核磁共振波谱分析方法，对苞叶连翘主要次生代谢产物进行分离和结构分析。材料和方法:对小苞草风干部位进行分析。单个化合物的分离采用开柱色谱法和填充有不同选择性吸附剂的玻璃柱进行——diion®HP-20 (Supelco)和Sephadex®LH-20 (GE Healthcare)——以及Kromasil®C18柱的制备级色谱法，检测波长为235 nm。以水和乙腈按5:95 ~ 50:50 v/v的比例混合，加入0.1%的三氟乙酸作为洗脱剂。采用高效薄层色谱法，硅胶60f254板(Merck)。单个化合物溶液的分析采用高效液相色谱法，采用prominent LC-20 (Shimadzu)仪器，SUPELCOSIL™LC-18色谱柱，在235 nm处检测。用Bruker Avance III 400 MHz核磁共振波谱仪对分离得到的单个化合物的结构进行了一维和二维核磁共振分析。结果:四种化合物分别来自С。从苞片植物中分离出异喹啉类生物碱黄连碱(1)和三种黄酮类化合物芦丁(2)、槲皮素-3- o -β- d -葡萄糖苷(3)和山奈酚-3- o -β- d -葡萄糖苷(4)。首次从苞片中分离到生物碱和黄酮类化合物，并利用核磁共振光谱对其结构进行了鉴定。С。苞片属植物应被认为是一种有前景的潜在生物活性物质来源。
{"title":"The Use of Spectroscopic Methods for Structural Elucidation of Individual Secondary Metabolites Isolated from the Aerial Parts of Corydalis bracteata","authors":"V. I. Toporkova, A. O. Ponkratova, A. K. Whaley, V. Luzhanin, M. U. Goncharov","doi":"10.30895/1991-2919-2022-12-1-56-64","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-56-64","url":null,"abstract":"Plants of the Corydalis (Papaveraceae) genus are widely used in oriental medicine and are known for their particularly rich content of biologically active substances. One of the species encountered in Russia, the large-flowered corydalis (Corydalis bracteata (Steph. ex Willd.) Pers.), is widespread in Western and Eastern Siberia, but none the less its chemical composition has not been properly studied yet.The aim of the study was to perform phytochemical analysis of Corydalis bracteata herb through isolation of the main secondary metabolites and elucidation of their structure, using modern chromatographic methods of analysis and NMR spectroscopy.Materials and methods: the analysis was performed for dried aerial parts of C. bracteata. The isolation of individual compounds was performed using open-column chromatography and glass columns packed with sorbents with different selectivity characteristics— Dianion® HP-20 (Supelco) and Sephadex® LH-20 (GE Healthcare)—as well as preparative-scale chromatography with a Kromasil® C18 column and detection at 235 nm. Water and acetonitrile mixed in the ratios 5:95–50:50 v/v with the addition of 0.1% trifluoroacetic acid were used as the eluents. The analysis of fractions before pooling was performed by high-performance thin-layer chromatography with Silica gel 60 F254 plates (Merck). The analysis of the individual compound solutions was performed by HPLC using a Prominence LC-20 (Shimadzu) instrument, a SUPELCOSIL™ LC-18 column, and detection at 235 nm. The structures of the isolated individual compounds were elucidated by one- and two-dimensional NMR spectroscopy using a Bruker Avance III 400 MHz NMR spectrometer.Results: four individual compounds from the С. bracteata aerial parts were isolated and analysed: an isoquinoline alkaloid— coptisine (1) and three flavonoids—rutin (2), quercetin-3-O-β-D-glucopyranoside (3), and kaempferol-3-O-β-D-glucopyranoside (4).Conclusions: as a result of the phytochemical analysis of the С. bracteata aerial parts, compounds of both alkaloid and flavonoid nature were isolated for the first time, and their structures were elucidated using NMR spectroscopy. С. bracteata should be considered as a promising potential source of biologically active substances.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87052260","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}
Pub Date : 2022-02-21DOI: 10.30895/1991-2919-2022-12-1-41-55
S. Ovsienko, V. M. Shchukin, E. A. Blinkova, N. E. Kuz’mina
Pumpkin seeds belong to the so-called native products. Their characteristic feature is that they can be consumed directly, without prior extraction of the starting material. All elemental toxicants contained in pumpkin seeds are transferred in full to the native product. Therefore, it is important to study specific aspects of elemental toxicant accumulation by pumpkin seeds.The aim of the study was to determine the content of heavy metals, As, and Al in pumpkin seed herbal substance and native products, and to assess the degree of accumulation of these elements, depending on the vegetation area.Materials and methods: the study evaluated pumpkin seed native products by Russian manufacturers as well as pumpkin seeds harvested in areas with different anthropogenic load. The sample preparation was performed by microwave digestion, and the determination of the elemental toxicants was perfomed by inductively coupled plasma mass spectrometry.Results: the pumpkin seeds were shown to contain essential, probably essential, potentially toxic, and toxic elements. The authors performed comparative analysis of the elemental composition of pumpkin seeds as well as seeds, grains, and beans of various oil-bearing, grain, and leguminous crops.Conclusions: the content of the specified elemental toxicants (As, Cd, Hg, Pb) in the tested samples of pumpkin seed herbal substance and herbal medicinal products did not exceed the limits established by the Russian Pharmacopoeia. The unspecified toxic elements were either absent in pumpkin seeds (Tl) or found in trace amounts (Al). The content of a number of essential elements (Zn, Fe, Mn, Cu, Mo, Cr) in pumpkin seeds was higher than in the seeds of many oil-bearing crops. The vegetation area had no significant influence on the content of the tested elements in the pumpkin seeds. Pumpkin seeds are capable of accumulating abnormally high amounts of Cd, Co, and Ni in areas with high environmental pollution.
{"title":"Determination of Heavy Metals, Arsenic, and Aluminum Content in Pumpkin Seed Herbal Substance and Native Products, by Inductively Coupled Plasma Mass Spectrometry","authors":"S. Ovsienko, V. M. Shchukin, E. A. Blinkova, N. E. Kuz’mina","doi":"10.30895/1991-2919-2022-12-1-41-55","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-41-55","url":null,"abstract":"Pumpkin seeds belong to the so-called native products. Their characteristic feature is that they can be consumed directly, without prior extraction of the starting material. All elemental toxicants contained in pumpkin seeds are transferred in full to the native product. Therefore, it is important to study specific aspects of elemental toxicant accumulation by pumpkin seeds.The aim of the study was to determine the content of heavy metals, As, and Al in pumpkin seed herbal substance and native products, and to assess the degree of accumulation of these elements, depending on the vegetation area.Materials and methods: the study evaluated pumpkin seed native products by Russian manufacturers as well as pumpkin seeds harvested in areas with different anthropogenic load. The sample preparation was performed by microwave digestion, and the determination of the elemental toxicants was perfomed by inductively coupled plasma mass spectrometry.Results: the pumpkin seeds were shown to contain essential, probably essential, potentially toxic, and toxic elements. The authors performed comparative analysis of the elemental composition of pumpkin seeds as well as seeds, grains, and beans of various oil-bearing, grain, and leguminous crops.Conclusions: the content of the specified elemental toxicants (As, Cd, Hg, Pb) in the tested samples of pumpkin seed herbal substance and herbal medicinal products did not exceed the limits established by the Russian Pharmacopoeia. The unspecified toxic elements were either absent in pumpkin seeds (Tl) or found in trace amounts (Al). The content of a number of essential elements (Zn, Fe, Mn, Cu, Mo, Cr) in pumpkin seeds was higher than in the seeds of many oil-bearing crops. The vegetation area had no significant influence on the content of the tested elements in the pumpkin seeds. Pumpkin seeds are capable of accumulating abnormally high amounts of Cd, Co, and Ni in areas with high environmental pollution.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"89 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84078265","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}
Pub Date : 2022-02-18DOI: 10.30895/1991-2919-2022-12-1-8-23
S. Moiseev, N. E. Kuz’mina, A. I. Luttseva
The ongoing development of the Pharmacopoeia of the Eurasian Economic Union and the current trend for harmonisation of the Russian Pharmacopoeia with the world leading pharmacopoeias suggest the necessity of studying how different pharmacopoeias use nuclear magnetic resonance (NMR) for quality control of medicinal products. The aim of the study was to compare the extent of medicine quality characteristics assessed by NMR in the Russian and foreign pharmacopoeias. The review summarises the experience of various national and world pharmacopoeias in using the NMR method for quality control of medicines and certification of pharmacopoeial reference materials. The comparative analysis covered the following quality parameters: active ingredient identification, determination of the composition of non-stoichiometric compounds, determination of the average polymer chain length in polymers and block copolymers, determination of the absolute content of the active ingredient, identification and quantification of impurities, polymorphism, and crystallinity. It was shown that the United States and Japanese Pharmacopoeias are leading the way in introducing the NMR method into pharmacopoeial analysis. There have been some positive trends in the introduction of the NMR method in the State Pharmacopoeia of the Russian Federation as well. It was concluded that changes are needed in the general chapters “Nuclear Magnetic Resonance Spectroscopy” and “Reference Standards” of the State Pharmacopoeia of the Russian Federation, 14th ed. in order to harmonise the texts with those of the Eurasian Pharmacopoeia and the European Pharmacopoeia and to allow for the possibility of direct identification of a substance by complex analysis of NMR spectral data, without comparing the test sample and the reference standard spectra. The NMR method should be included in the list of absolute methods used for determination of purity of primary chemical reference substances during certification.
{"title":"NMR as Used in the Russian and Foreign Pharmacopoeias for Quality Control of Medicinal Products","authors":"S. Moiseev, N. E. Kuz’mina, A. I. Luttseva","doi":"10.30895/1991-2919-2022-12-1-8-23","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-8-23","url":null,"abstract":"The ongoing development of the Pharmacopoeia of the Eurasian Economic Union and the current trend for harmonisation of the Russian Pharmacopoeia with the world leading pharmacopoeias suggest the necessity of studying how different pharmacopoeias use nuclear magnetic resonance (NMR) for quality control of medicinal products. The aim of the study was to compare the extent of medicine quality characteristics assessed by NMR in the Russian and foreign pharmacopoeias. The review summarises the experience of various national and world pharmacopoeias in using the NMR method for quality control of medicines and certification of pharmacopoeial reference materials. The comparative analysis covered the following quality parameters: active ingredient identification, determination of the composition of non-stoichiometric compounds, determination of the average polymer chain length in polymers and block copolymers, determination of the absolute content of the active ingredient, identification and quantification of impurities, polymorphism, and crystallinity. It was shown that the United States and Japanese Pharmacopoeias are leading the way in introducing the NMR method into pharmacopoeial analysis. There have been some positive trends in the introduction of the NMR method in the State Pharmacopoeia of the Russian Federation as well. It was concluded that changes are needed in the general chapters “Nuclear Magnetic Resonance Spectroscopy” and “Reference Standards” of the State Pharmacopoeia of the Russian Federation, 14th ed. in order to harmonise the texts with those of the Eurasian Pharmacopoeia and the European Pharmacopoeia and to allow for the possibility of direct identification of a substance by complex analysis of NMR spectral data, without comparing the test sample and the reference standard spectra. The NMR method should be included in the list of absolute methods used for determination of purity of primary chemical reference substances during certification.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79682135","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}
Pub Date : 2022-02-11DOI: 10.30895/1991-2919-2022-12-1-65-78
V. M. Shchukin, N. E. Kuz’mina, Yu. N. Shvetsova, A. I. Luttseva
When the approach to quality control of herbal substances (HSs) and herbal medicinal products (HMPs) changed from determination of the total content of heavy metals by calorimetry to selective determination by spectrometric techniques, many manufacturers of such products failed to meet the new requirements in their registration dossiers. Test procedures submitted by manufacturers often need to be clarified, and validation protocols often lack data.The aim of the study was to provide recommendations to HS and HMP manufacturers on the choice of test methods, materials, reagents, methods of organic matrix mineralisation, and main validation parameters, as well as recommendations on validation of the procedure for elemental toxicants determination, and preparation of the “Heavy metals and arsenic” part of the regulatory submission.Materials and methods: the study included analysis and systematisation of scientific literature, requirements of the Russian and foreign pharmacopoeias, guidelines, manuals on instrumental methods of analysis, and first-hand experience in elemental analysis of various types of HSs and HMPs.Results: the authors formulated recommendations on the choice of sample mineralisation conditions for quantification of elemental impurities in biological products, and substantiated requirements for the reagents, materials, and equipment. The paper compares different methods of elemental analysis. It was demonstrated that the main mistakes made by manufacturers stem from disregard to the organic matrix effect on the measurement results and lack of agreement between the impurity concentration being determined and the range of the calibration curve used. The paper gives acceptance criteria for validation parameters of test procedures for heavy metals and arsenic determination in HSs and HMPs.Conclusions: it is not correct to use reference standards containing heavy metals as inorganic salts not bound to organic compounds, for HS and HMP analysis. The criteria given in the European Pharmacopoeia and the United State Pharmacopoeia can be used for a number of validation parameters, when they are not included in the Russian Pharmacopoeia.
{"title":"Development and Validation of Procedures for Determination of Elemental Toxicants in Herbal Substances and Herbal Medicinal Products","authors":"V. M. Shchukin, N. E. Kuz’mina, Yu. N. Shvetsova, A. I. Luttseva","doi":"10.30895/1991-2919-2022-12-1-65-78","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-65-78","url":null,"abstract":"When the approach to quality control of herbal substances (HSs) and herbal medicinal products (HMPs) changed from determination of the total content of heavy metals by calorimetry to selective determination by spectrometric techniques, many manufacturers of such products failed to meet the new requirements in their registration dossiers. Test procedures submitted by manufacturers often need to be clarified, and validation protocols often lack data.The aim of the study was to provide recommendations to HS and HMP manufacturers on the choice of test methods, materials, reagents, methods of organic matrix mineralisation, and main validation parameters, as well as recommendations on validation of the procedure for elemental toxicants determination, and preparation of the “Heavy metals and arsenic” part of the regulatory submission.Materials and methods: the study included analysis and systematisation of scientific literature, requirements of the Russian and foreign pharmacopoeias, guidelines, manuals on instrumental methods of analysis, and first-hand experience in elemental analysis of various types of HSs and HMPs.Results: the authors formulated recommendations on the choice of sample mineralisation conditions for quantification of elemental impurities in biological products, and substantiated requirements for the reagents, materials, and equipment. The paper compares different methods of elemental analysis. It was demonstrated that the main mistakes made by manufacturers stem from disregard to the organic matrix effect on the measurement results and lack of agreement between the impurity concentration being determined and the range of the calibration curve used. The paper gives acceptance criteria for validation parameters of test procedures for heavy metals and arsenic determination in HSs and HMPs.Conclusions: it is not correct to use reference standards containing heavy metals as inorganic salts not bound to organic compounds, for HS and HMP analysis. The criteria given in the European Pharmacopoeia and the United State Pharmacopoeia can be used for a number of validation parameters, when they are not included in the Russian Pharmacopoeia.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86030405","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}
Pub Date : 2022-02-07DOI: 10.30895/1991-2919-2022-12-1-110-111
O. Shapovalova, N. P. Neugodova
Product specification files for parenteral medicines, as well as for active ingredients used in their production, have to include the “Bacterial endotoxins” parameter that controls the content of pyrogenic impurities. The experts of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation proposed recommendations for calculation and selection of the bacterial endotoxin limit, which will help applicants to include correct requirements for bacterial endotoxin limits in their product specification files. The proposed algorithm for the selection of bacterial endotoxin limits will make it possible to reduce the risk of pyrogenic reactions in patients and ensure safe use of medicinal products.
{"title":"Methodology for Calculating Bacterial Endotoxin Limits","authors":"O. Shapovalova, N. P. Neugodova","doi":"10.30895/1991-2919-2022-12-1-110-111","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-110-111","url":null,"abstract":"Product specification files for parenteral medicines, as well as for active ingredients used in their production, have to include the “Bacterial endotoxins” parameter that controls the content of pyrogenic impurities. The experts of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation proposed recommendations for calculation and selection of the bacterial endotoxin limit, which will help applicants to include correct requirements for bacterial endotoxin limits in their product specification files. The proposed algorithm for the selection of bacterial endotoxin limits will make it possible to reduce the risk of pyrogenic reactions in patients and ensure safe use of medicinal products.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85664956","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}
Pub Date : 2022-01-31DOI: 10.30895/1991-2919-2022-12-1-90-109
A. Durnev, A. Zhanataev
Genotoxic lesions are not only a cause of genetic pathologies and cancer, but also the most common and significant factor of the etiopathology of cardiovascular and neurodegenerative disorders, reproductive losses, infertility, and aging. This requires careful monitoring of the use of potential genotoxicants including medicinal products (MPs), which are a group of compounds intentionally and routinely used by humans. Genotoxicity assesment is highly essential in preclinical drug safety studies. The aim of the study was to analyse the current situation and reveal possible ways of addressing methodological and regulatory issues in genotoxicology to enable proper conduction of drug safety preclinical studies. The article summarises basic concepts of the modern genetic toxicology development and highlights the history of research aimed at identifying mutagenic, clastogenic, and aneugenic effects. The authors analyse regulatory aspects of genotoxicological studies of MPs and consider issues of improving the strategy for genotoxicity testing. The paper gives information about the genotoxicity tests approved for MPs, recommendations for interchangeability of tests in relation to particular study characteristics. The authors carried out a comparative analysis of the tests’ pros and cons with an emphasis that the study of each MP is a separate scientific task. They discuss interpretation of results and prediction of MP carcinogenic potential in genotoxicological studies. Recommendations are given for the optimisation of the MP genotoxicity assessment strategy, considering its partial integration into general toxicity studies. The article stresses the urgent need to develop registration methods for genotoxic events in germ cells, assesses the prospects of new tests, and reviews new trends in drug genotoxicology fundamental research.
{"title":"Relevant Aspects of Drug Genetic Toxicology","authors":"A. Durnev, A. Zhanataev","doi":"10.30895/1991-2919-2022-12-1-90-109","DOIUrl":"https://doi.org/10.30895/1991-2919-2022-12-1-90-109","url":null,"abstract":"Genotoxic lesions are not only a cause of genetic pathologies and cancer, but also the most common and significant factor of the etiopathology of cardiovascular and neurodegenerative disorders, reproductive losses, infertility, and aging. This requires careful monitoring of the use of potential genotoxicants including medicinal products (MPs), which are a group of compounds intentionally and routinely used by humans. Genotoxicity assesment is highly essential in preclinical drug safety studies. The aim of the study was to analyse the current situation and reveal possible ways of addressing methodological and regulatory issues in genotoxicology to enable proper conduction of drug safety preclinical studies. The article summarises basic concepts of the modern genetic toxicology development and highlights the history of research aimed at identifying mutagenic, clastogenic, and aneugenic effects. The authors analyse regulatory aspects of genotoxicological studies of MPs and consider issues of improving the strategy for genotoxicity testing. The paper gives information about the genotoxicity tests approved for MPs, recommendations for interchangeability of tests in relation to particular study characteristics. The authors carried out a comparative analysis of the tests’ pros and cons with an emphasis that the study of each MP is a separate scientific task. They discuss interpretation of results and prediction of MP carcinogenic potential in genotoxicological studies. Recommendations are given for the optimisation of the MP genotoxicity assessment strategy, considering its partial integration into general toxicity studies. The article stresses the urgent need to develop registration methods for genotoxic events in germ cells, assesses the prospects of new tests, and reviews new trends in drug genotoxicology fundamental research.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87691520","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}
Pub Date : 2021-12-02DOI: 10.30895/1991-2919-2021-11-4-273-275
O. A. Vaganova
“Glycan Profile” is a necessary part of manufacturers’ product specification files for monoclonal antibody active ingredients or final products and erythropoietin active ingredients. The expert of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation provides recommendations for a step-by-step presentation of the test procedure, which will allow applicants to align product specification files for Russian- and foreign-produced medicinal products, help experts to minimise or eliminate the need to request additional information from applicants, and will contribute to timely batch release of medicinal products.
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Pub Date : 2021-12-02DOI: 10.30895/1991-2919-2021-11-4-276-277
O. A. Vaganova
‘Identification. Peptide mapping’ is a necessary part of manufacturers’ product specification files for therapeutic proteins (active ingredients and final products of monoclonal antibodies, filgrastims, erythropoietins). The expert of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation provides recommendations for a step-by-step presentation of the test procedure, which will allow applicants to align product specification files for Russian- and foreign-produced medicinal products, help experts to minimise or eliminate the need to request additional information from applicants, and will contribute to timely batch release of medicinal products.
{"title":"Recommendations for the Contents of the “Peptide Mapping” Part of a Product Specification File","authors":"O. A. Vaganova","doi":"10.30895/1991-2919-2021-11-4-276-277","DOIUrl":"https://doi.org/10.30895/1991-2919-2021-11-4-276-277","url":null,"abstract":"‘Identification. Peptide mapping’ is a necessary part of manufacturers’ product specification files for therapeutic proteins (active ingredients and final products of monoclonal antibodies, filgrastims, erythropoietins). The expert of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation provides recommendations for a step-by-step presentation of the test procedure, which will allow applicants to align product specification files for Russian- and foreign-produced medicinal products, help experts to minimise or eliminate the need to request additional information from applicants, and will contribute to timely batch release of medicinal products.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87529620","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}
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