Pub Date : 2020-08-27DOI: 10.30895/1991-2919-2020-10-3-148-151
B. Romanov
The review compares individual case safety reports (ICSRs) for hydroxychloroquine, favipiravir, and the lopinavir/ ritonavir combination registered in the VigiBase global database during 6 months in 2019 and the same period in 2020 which coincides with the global “first wave”. The aim of the study was to identify specific aspects of using these drugs for the treatment of COVID-19. There was an increase in the use of hydroxychloroquine, favipiravir, and the lopinavir/ritonavir combination during the pandemic, which was accompanied by a significant deterioration in the quantitative and qualitative safety profiles of these drugs. The review summarises the main risks of using these drugs for COVID-19 treatment and highlights the need for revision of the recommendations for their use in the context of the new coronavirus disease.
{"title":"Safety of Hydroxychloroquine, Favipiravir, and the Combination of Lopinavir and Ritonavir in the Treatment of the “First Wave” of the New Coronavirus Infection COVID-19","authors":"B. Romanov","doi":"10.30895/1991-2919-2020-10-3-148-151","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-3-148-151","url":null,"abstract":"The review compares individual case safety reports (ICSRs) for hydroxychloroquine, favipiravir, and the lopinavir/ ritonavir combination registered in the VigiBase global database during 6 months in 2019 and the same period in 2020 which coincides with the global “first wave”. The aim of the study was to identify specific aspects of using these drugs for the treatment of COVID-19. There was an increase in the use of hydroxychloroquine, favipiravir, and the lopinavir/ritonavir combination during the pandemic, which was accompanied by a significant deterioration in the quantitative and qualitative safety profiles of these drugs. The review summarises the main risks of using these drugs for COVID-19 treatment and highlights the need for revision of the recommendations for their use in the context of the new coronavirus disease.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83964422","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-137-141
T. A. Batuashvili, L. V. Simutenko, N. P. Neugodova, P. V. Shadrin
In order to harmonise national and foreign requirements for quality control of medicinal products, a second variant of the test method, which complies with the requirements of the European Pharmacopoeia, was included into the general monograph OFS.1.2.4.0008.18 “Test for depressor substances”. The aim of the study was to compare the two variants of the in vivo test method that uses cats for determination of depressor substances in medicinal products and to develop recommendations for the use of these two variants of the test method. The comparative analysis of the two ways of determining impurities that lower blood pressure revealed different approaches to performing the test and to testing an animal's sensitivity to the reference solution (histamine dihydrochloride). It was demonstrated that different concentrations, volumes, and doses of medicinal products are used to assess the results of testing performed by variants 1 and 2 of the test method according to the pharmacopoeial requirements. Based on the established differences in the methodological approach to determination of depressor substances in medicinal products, the authors developed recommendations for each of the test variants. The inclusion of two variants of the test method in the general monograph provides an opportunity to evaluate the quality of medicinal products under the most appropriate conditions and, consequently, to improve the validity of test results.
{"title":"Methodological Approaches to Determination of Depressor Substances","authors":"T. A. Batuashvili, L. V. Simutenko, N. P. Neugodova, P. V. Shadrin","doi":"10.30895/1991-2919-2020-10-2-137-141","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-137-141","url":null,"abstract":"In order to harmonise national and foreign requirements for quality control of medicinal products, a second variant of the test method, which complies with the requirements of the European Pharmacopoeia, was included into the general monograph OFS.1.2.4.0008.18 “Test for depressor substances”. The aim of the study was to compare the two variants of the in vivo test method that uses cats for determination of depressor substances in medicinal products and to develop recommendations for the use of these two variants of the test method. The comparative analysis of the two ways of determining impurities that lower blood pressure revealed different approaches to performing the test and to testing an animal's sensitivity to the reference solution (histamine dihydrochloride). It was demonstrated that different concentrations, volumes, and doses of medicinal products are used to assess the results of testing performed by variants 1 and 2 of the test method according to the pharmacopoeial requirements. Based on the established differences in the methodological approach to determination of depressor substances in medicinal products, the authors developed recommendations for each of the test variants. The inclusion of two variants of the test method in the general monograph provides an opportunity to evaluate the quality of medicinal products under the most appropriate conditions and, consequently, to improve the validity of test results.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84789052","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-96-110
O. Bezborodova, A. Pankratov, E. Nemtsova, Yu. B. Venediktova, M. Vorontsova, G. N. Engalycheva, R. Syubaev
The decoding of the DNA structure and development of new molecular methods of its analysis, as well as identification of specific genomic changes responsible for malignant transformation, have become the turning points in elaboration of novel anti-tumour drugs directed against molecular and genetic targets of tumor growth. Transition from empirical screening of agents inhibiting tumour cell proliferation to molecule-targeted analytical methods has raised a number of serious methodological issues regarding preclinical evaluation of novel medicines. The objective of this paper was to analyse general principles and features of preclinical efficacy and safety studies of different classes of modern anti-tumour drugs with a view to improve existing national guidelines. The paper reviews various aspects of preclinical studies of different classes of anti-tumour drugs (small molecule chemotherapy drugs, hormones and hormone antagonists, alkylating agents and antimetabolites, microbial and herbal medicines, as well as monoclonal antibodies). The article explores general principles of studying the drugs’ pharmacological activity in vitro, ex vivo, and in vivo, and evaluating their pharmacokinetic parameters. It describes various methods and models of research, summarises specific aspects of determination of genotoxicity, carcinogenicity, reproductive toxicity, mutagenicity, acute and chronic toxicity of various groups of medicines. It also lists criteria for selecting drug doses for toxicokinetic studies. The need for harmonisation of national requirements for conducting preclinical studies with the European standards entails alignment of terminology and further development of general algorithms for selecting doses and determining the necessary scope of research. The use of biomarkers in preclinical studies will make it possible to exclude inefficient compounds from further research.
{"title":"Anti-Tumour Drugs: Planning Preclinical Efficacy and Safety Studies","authors":"O. Bezborodova, A. Pankratov, E. Nemtsova, Yu. B. Venediktova, M. Vorontsova, G. N. Engalycheva, R. Syubaev","doi":"10.30895/1991-2919-2020-10-2-96-110","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-96-110","url":null,"abstract":"The decoding of the DNA structure and development of new molecular methods of its analysis, as well as identification of specific genomic changes responsible for malignant transformation, have become the turning points in elaboration of novel anti-tumour drugs directed against molecular and genetic targets of tumor growth. Transition from empirical screening of agents inhibiting tumour cell proliferation to molecule-targeted analytical methods has raised a number of serious methodological issues regarding preclinical evaluation of novel medicines. The objective of this paper was to analyse general principles and features of preclinical efficacy and safety studies of different classes of modern anti-tumour drugs with a view to improve existing national guidelines. The paper reviews various aspects of preclinical studies of different classes of anti-tumour drugs (small molecule chemotherapy drugs, hormones and hormone antagonists, alkylating agents and antimetabolites, microbial and herbal medicines, as well as monoclonal antibodies). The article explores general principles of studying the drugs’ pharmacological activity in vitro, ex vivo, and in vivo, and evaluating their pharmacokinetic parameters. It describes various methods and models of research, summarises specific aspects of determination of genotoxicity, carcinogenicity, reproductive toxicity, mutagenicity, acute and chronic toxicity of various groups of medicines. It also lists criteria for selecting drug doses for toxicokinetic studies. The need for harmonisation of national requirements for conducting preclinical studies with the European standards entails alignment of terminology and further development of general algorithms for selecting doses and determining the necessary scope of research. The use of biomarkers in preclinical studies will make it possible to exclude inefficient compounds from further research.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88917394","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-82-88
N. P. Neugodova, E. O. Stepanyuk, G. A. Sapozhnikova, E. I. Sakanyan, M. S. Ryabtseva
For over 60 years, the Abnormal Toxicity Test (ATT) has been used as an important tool in safety control of some parenteral and veterinary products made from biological materials. In 2017, some of the members of the Pharmacopoeial Committee of the Eurasian Economic Union (EAEU) proposed not to include the ATT in the draft monographs of the EAEU Pharmacopoeia based on the decision of the European Pharmacopoeia Commission to suppress the test. However, this may not be achieved in Russia at this point, because some production sites that manufacture medicinal products for human and veterinary use have not fully implemented GMP principles yet. The main aim of the ATT is to detect any toxicity above the pre-determined acceptable level. The unacceptable toxicity levels can manifest themselves in higher mortality rates or unexpected intoxication effects in laboratory animals. This test makes it possible to detect abnormal (high) toxicity of a medicinal product which may be associated with degradation products or undesirable impurities resulting from changes of the production technology, which are not mentioned in specification documents related to production, transportation, and storage. In 2016—2017 12 batches of veterinary products, including vaccines and sera, were found to be noncompliant, and the Federal Service for Surveillance in Healthcare rejected 16 batches of medicinal products in 2016—2019. The aim of the study was to analyse current approaches to the ATT in the Russian and foreign pharmacopeias, and to develop a programme for phasing out the ATT use depending on the nature and pharmacological properties of medicinal products. Comparative analysis of the monographs of the world leading pharmacopeias showed that the State Pharmacopoeia of the Russian Federation has the most stringent test conditions. As an alternative to suppressing the ATT the authors suggest a phased approach to reduce the use of this test. They determined groups of medicinal products whose pharmacological properties allow for the suppression of the test. The proposed approach to phasing out the use of ATT will make it possible to use the test effectively and reduce the number of performed tests, but will still ensure drug safety. The suppression of the ATT can not be achieved without a comprehensive detailed research by quality control specialists and further discussion by all interested parties.
{"title":"Current Approaches to the Abnormal Toxicity Test","authors":"N. P. Neugodova, E. O. Stepanyuk, G. A. Sapozhnikova, E. I. Sakanyan, M. S. Ryabtseva","doi":"10.30895/1991-2919-2020-10-2-82-88","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-82-88","url":null,"abstract":"For over 60 years, the Abnormal Toxicity Test (ATT) has been used as an important tool in safety control of some parenteral and veterinary products made from biological materials. In 2017, some of the members of the Pharmacopoeial Committee of the Eurasian Economic Union (EAEU) proposed not to include the ATT in the draft monographs of the EAEU Pharmacopoeia based on the decision of the European Pharmacopoeia Commission to suppress the test. However, this may not be achieved in Russia at this point, because some production sites that manufacture medicinal products for human and veterinary use have not fully implemented GMP principles yet. The main aim of the ATT is to detect any toxicity above the pre-determined acceptable level. The unacceptable toxicity levels can manifest themselves in higher mortality rates or unexpected intoxication effects in laboratory animals. This test makes it possible to detect abnormal (high) toxicity of a medicinal product which may be associated with degradation products or undesirable impurities resulting from changes of the production technology, which are not mentioned in specification documents related to production, transportation, and storage. In 2016—2017 12 batches of veterinary products, including vaccines and sera, were found to be noncompliant, and the Federal Service for Surveillance in Healthcare rejected 16 batches of medicinal products in 2016—2019. The aim of the study was to analyse current approaches to the ATT in the Russian and foreign pharmacopeias, and to develop a programme for phasing out the ATT use depending on the nature and pharmacological properties of medicinal products. Comparative analysis of the monographs of the world leading pharmacopeias showed that the State Pharmacopoeia of the Russian Federation has the most stringent test conditions. As an alternative to suppressing the ATT the authors suggest a phased approach to reduce the use of this test. They determined groups of medicinal products whose pharmacological properties allow for the suppression of the test. The proposed approach to phasing out the use of ATT will make it possible to use the test effectively and reduce the number of performed tests, but will still ensure drug safety. The suppression of the ATT can not be achieved without a comprehensive detailed research by quality control specialists and further discussion by all interested parties.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75378688","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-89-95
G. I. Gorodetskaya, V. Arkhipov, E. Melnikov, T. Rodina
Rational use of glybenclamide products in the treatment of patients with type 2 diabetes remains a high-priority task. The paper offers a summary of the main groups of glibenclamide drugs and describes pharmacogenetics of glybenclamide. Glibenclamide is metabolized by the enzyme cytochrome P450 2C9 (CYP2C9). Individuals with genetically determined low CYP2C9 activity are at an increased risk of hypoglycaemia. Carriers of CYP2C9*3 and CYP2C9*2 alleles tend to have higher concentrations of glybenclamide in blood and increased insulin secretion. Pharmacogenetic testing of patients and drug concentration monitoring using HPLC-MS can help reduce the risk of hypoglycemia during glibenclamide treatment. Based on literature review the authors selected the method characterised by a simple sample preparation procedure, short analysis time, and a wide analytical range for the substances being determined. This method can be useful both for bioequivalence studies and evaluation of glibenclamide products interchangeability. Glibenclamide pharmacokinetics is characterised by high interindividual variability. This may lead to both an increased risk of hypoglycemia and drug inefficacy, therefore, when prescribing glibenclamide, a physician should carefully control the efficacy and safety of drug therapy.
{"title":"Therapeutic Drug Monitoring, CYP2C9 Genotyping and Phenotyping in the Treatment of Diabetes with Glibenclamide Products","authors":"G. I. Gorodetskaya, V. Arkhipov, E. Melnikov, T. Rodina","doi":"10.30895/1991-2919-2020-10-2-89-95","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-89-95","url":null,"abstract":"Rational use of glybenclamide products in the treatment of patients with type 2 diabetes remains a high-priority task. The paper offers a summary of the main groups of glibenclamide drugs and describes pharmacogenetics of glybenclamide. Glibenclamide is metabolized by the enzyme cytochrome P450 2C9 (CYP2C9). Individuals with genetically determined low CYP2C9 activity are at an increased risk of hypoglycaemia. Carriers of CYP2C9*3 and CYP2C9*2 alleles tend to have higher concentrations of glybenclamide in blood and increased insulin secretion. Pharmacogenetic testing of patients and drug concentration monitoring using HPLC-MS can help reduce the risk of hypoglycemia during glibenclamide treatment. Based on literature review the authors selected the method characterised by a simple sample preparation procedure, short analysis time, and a wide analytical range for the substances being determined. This method can be useful both for bioequivalence studies and evaluation of glibenclamide products interchangeability. Glibenclamide pharmacokinetics is characterised by high interindividual variability. This may lead to both an increased risk of hypoglycemia and drug inefficacy, therefore, when prescribing glibenclamide, a physician should carefully control the efficacy and safety of drug therapy.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"71 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91023218","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-111-120
А. Bogdanov, E. Gorbunova, D. Goryachev, E. V. Petraneva
Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field. To date, many international recommendations related to planning, conduct of clinical trials, and analysis of their results, have been updated. Considerable experience has been gained with clinical trials of medicines intended for the treatment of Crohn’s disease. Therefore, the methodological approach to the planning of pivotal clinical studies needs to be reviewed. The aim of the study was to develop requirements for planning and expert evaluation of clinical trials conducted with the aim of obtaining marketing authorisation for medicinal products for the treatment of Crohn’s disease. The paper analyses regulations, recommendations, and scientific literature on the treatment of Crohn’s disease and describes the methodology for planning clinical trials. It describes the evolution of approaches to clinical research planning since biological medicines appeared. The authors substantiate the need for an integrated concept of clinical research, which covers goals, estimated therapeutic effect, design, and choice of the statistical analysis method. They also provide scientific arguments in favour of a combined primary endpoint including endoscopic remission and the assessment of treatment results by the patient. The paper lists patient eligibility criteria in terms of “inducing and/or maintaining remission of the disease”. The authors analyse the main intercurrent events, their influence on the therapeutic effect, and propose approaches to the planning of endpoints, including assessment of intercurrent events. The paper highlights the fact that the principles of planning and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation.
{"title":"Current Approaches to Planning and Conducting Clinical Trials of Medicinal Products for the Treatment of Crohn's Disease","authors":"А. Bogdanov, E. Gorbunova, D. Goryachev, E. V. Petraneva","doi":"10.30895/1991-2919-2020-10-2-111-120","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-111-120","url":null,"abstract":"Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field. To date, many international recommendations related to planning, conduct of clinical trials, and analysis of their results, have been updated. Considerable experience has been gained with clinical trials of medicines intended for the treatment of Crohn’s disease. Therefore, the methodological approach to the planning of pivotal clinical studies needs to be reviewed. The aim of the study was to develop requirements for planning and expert evaluation of clinical trials conducted with the aim of obtaining marketing authorisation for medicinal products for the treatment of Crohn’s disease. The paper analyses regulations, recommendations, and scientific literature on the treatment of Crohn’s disease and describes the methodology for planning clinical trials. It describes the evolution of approaches to clinical research planning since biological medicines appeared. The authors substantiate the need for an integrated concept of clinical research, which covers goals, estimated therapeutic effect, design, and choice of the statistical analysis method. They also provide scientific arguments in favour of a combined primary endpoint including endoscopic remission and the assessment of treatment results by the patient. The paper lists patient eligibility criteria in terms of “inducing and/or maintaining remission of the disease”. The authors analyse the main intercurrent events, their influence on the therapeutic effect, and propose approaches to the planning of endpoints, including assessment of intercurrent events. The paper highlights the fact that the principles of planning and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73698131","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-129-136
N. Antonova, I. M. Morgunov, S. P. Prokhvatilova, E. Shefer, A. Kalinin, T. A. Golomazova
Specialists in pharmacognosy are facing an important task of improving quality control methods for combination herbal medicinal products in order to enable reliable assessment of the content of active substances that are responsible for the drug’s pharmacological effect.The aim of the study was to investigate the possibility of using the European Pharmacopoeia method to determine the total content of anthracene derivatives in the antihaemorrhoidal medicinal herb mixture Proctophytol® and to propose limit values for the total content of anthracene derivatives.Materials and methods: individual mixture components containing anthracene derivatives, such as senna leaves and frangula bark, as well as model mixtures containing these individual components in a 1:1 ratio, and a model mixture imitating Proctophytol® were used in the study. The determination of the anthracene derivatives content was carried out using spectrophotometry.Results: it was demonstrated that the European Pharmacopoeia method could be used to assess the quality of Proctophytol® in terms of anthracene derivatives total content. The spectrophotometric method described in the European Pharmacopoeia has advantages over the methods described in manufacturer specifications for Russian products, because it allows for thorough extraction of the active substances and is standardized for anthracene derivatives.Conclusions: the European Pharmacopoeia method was adjusted to determine anthracene derivatives in the medicinal herb mixture Proctophytol®. It was proposed to use 70% ethanol instead of 70% methanol as extraction solvent. The authors identified optimum sample weights and test solution dilutions, and calculated and verified the limit for anthracene derivatives content—“Not less than 1.9%”. The adjusted method can be recommended for inclusion in the monographs of the State Pharmacopoeia of the Russian Federation for medicinal herb mixtures similar to Proctophytol®.
{"title":"Determination of Anthracene Derivatives in the Antihaemorrhoidal Medicinal Herb Mixture Proctophytol® Using the European Pharmacopoeia Method","authors":"N. Antonova, I. M. Morgunov, S. P. Prokhvatilova, E. Shefer, A. Kalinin, T. A. Golomazova","doi":"10.30895/1991-2919-2020-10-2-129-136","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-129-136","url":null,"abstract":"Specialists in pharmacognosy are facing an important task of improving quality control methods for combination herbal medicinal products in order to enable reliable assessment of the content of active substances that are responsible for the drug’s pharmacological effect.The aim of the study was to investigate the possibility of using the European Pharmacopoeia method to determine the total content of anthracene derivatives in the antihaemorrhoidal medicinal herb mixture Proctophytol® and to propose limit values for the total content of anthracene derivatives.Materials and methods: individual mixture components containing anthracene derivatives, such as senna leaves and frangula bark, as well as model mixtures containing these individual components in a 1:1 ratio, and a model mixture imitating Proctophytol® were used in the study. The determination of the anthracene derivatives content was carried out using spectrophotometry.Results: it was demonstrated that the European Pharmacopoeia method could be used to assess the quality of Proctophytol® in terms of anthracene derivatives total content. The spectrophotometric method described in the European Pharmacopoeia has advantages over the methods described in manufacturer specifications for Russian products, because it allows for thorough extraction of the active substances and is standardized for anthracene derivatives.Conclusions: the European Pharmacopoeia method was adjusted to determine anthracene derivatives in the medicinal herb mixture Proctophytol®. It was proposed to use 70% ethanol instead of 70% methanol as extraction solvent. The authors identified optimum sample weights and test solution dilutions, and calculated and verified the limit for anthracene derivatives content—“Not less than 1.9%”. The adjusted method can be recommended for inclusion in the monographs of the State Pharmacopoeia of the Russian Federation for medicinal herb mixtures similar to Proctophytol®.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76832465","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 : 2020-06-20DOI: 10.30895/1991-2919-2020-10-2-121-128
V. Kosman, M. V. Karlina, O. Pozharitskaya
The HPLC-UV method is widely used for quantitative analysis of drug substances found in biological samples obtained in pharmacokinetics studies, bioequivalence studies, or during therapeutic drug monitoring. The main limitation is associated with a significant background effect of biological matrixes, limiting the sensitivity of HPLC-UV methods.The aim of the study was to evaluate sample preparation and chromatographic conditions in terms of background signal level during HPLC-UV analysis of blood plasma.Material and methods: three types of blood plasma (rat, rabbit and human), three chromatographic modes, and three detection wavelengths were used to assess the effect of the precipitation agent, centrifuge conditions, and the inclusion of the solid-phase extraction (SPE) step into the sample preparation procedure on the background signal level during HPLC-UV analysis.Results. It was established that the background signal was practically unaffected by the chromatographic mode, centrifugation intensity, or introduction of the SPE step. The background signal levels for human and rabbit blood plasma tended to be lower than that for rat blood plasma. The factors that had the greatest effect on the background signal level were the choice of the precipitation agent during sample preparation, and the detection wavelength. It was shown that acetonitrile is preferable to methanol, and that the near UV region should be avoided.Conclusions. The identified key aspects of sample preparation procedures and chromatographic conditions can be used in the development and validation of bioanalytical methods for preclinical and clinical studies.
{"title":"Effect of Sample Preparation and Chromatographic Conditions on Background Signal","authors":"V. Kosman, M. V. Karlina, O. Pozharitskaya","doi":"10.30895/1991-2919-2020-10-2-121-128","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-2-121-128","url":null,"abstract":"The HPLC-UV method is widely used for quantitative analysis of drug substances found in biological samples obtained in pharmacokinetics studies, bioequivalence studies, or during therapeutic drug monitoring. The main limitation is associated with a significant background effect of biological matrixes, limiting the sensitivity of HPLC-UV methods.The aim of the study was to evaluate sample preparation and chromatographic conditions in terms of background signal level during HPLC-UV analysis of blood plasma.Material and methods: three types of blood plasma (rat, rabbit and human), three chromatographic modes, and three detection wavelengths were used to assess the effect of the precipitation agent, centrifuge conditions, and the inclusion of the solid-phase extraction (SPE) step into the sample preparation procedure on the background signal level during HPLC-UV analysis.Results. It was established that the background signal was practically unaffected by the chromatographic mode, centrifugation intensity, or introduction of the SPE step. The background signal levels for human and rabbit blood plasma tended to be lower than that for rat blood plasma. The factors that had the greatest effect on the background signal level were the choice of the precipitation agent during sample preparation, and the detection wavelength. It was shown that acetonitrile is preferable to methanol, and that the near UV region should be avoided.Conclusions. The identified key aspects of sample preparation procedures and chromatographic conditions can be used in the development and validation of bioanalytical methods for preclinical and clinical studies.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82983695","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 : 2020-02-26DOI: 10.30895/1991-2919-2020-10-1-63-76
N. E. Kuz’mina, S. Moiseev, A. I. Luttseva
The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.Materials and methods: 1H and 13C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by 1H-1H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.
{"title":"The Problem of Dynamic Process Manifestation in Identification of Organic Compounds by NMR Spectroscopy","authors":"N. E. Kuz’mina, S. Moiseev, A. I. Luttseva","doi":"10.30895/1991-2919-2020-10-1-63-76","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-1-63-76","url":null,"abstract":"The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.Materials and methods: 1H and 13C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by 1H-1H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73663620","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 : 2020-02-26DOI: 10.30895/1991-2919-2020-10-1-29-40
L. N. Frolova, E. L. Kovaleva, E. I. Sakanyan, V. Y. Kuteynikov, V. V. Shelestova, M. A. Cheremisina
. The study of the nomenclature of officinal herbal substances and medicinal plants is important for finding potential ways of expanding the existing range of raw materials used in the production of herbal medicinal products. The authors com-pared the standards included into the State Pharmacopoeia of the Russian Federation, national pharmacopoeias of the Member States of the Eurasian Economic Union, and the world’s leading pharmacopoeias with a focus on herbal substances, medicinal plants, morphological groups of herbal substances, and the proportion of cultivated medicinal plants versus wild medicinal plants. The paper describes historical changes in the nomenclature of herbal substances included in various editions of the Russian Pharmacopoeia. The analysis of the State Register of Medicinal Products revealed the most common morphological groups of herbal substances used in Russia for the production of herbal medicinal products. The paper provides information about the largest Russian manufacturers of herbal medicinal products that preserve national traditions and develop new dosa- ge forms. It outlines ways of improving standardisation of herbal substances using current test methods for characterisation of biologically active substances. The analysis helped to identify potential ways of expanding the range of herbal raw materials: the use of botanical species closely related to officinal ones, increasing the number of morphological groups of substances by inte-grated use of harvested plants, the inclusion of non-officinal botanical species that have a long history of use in the traditional medicine into the Russian list of officinal species. the individual data analysis interpretation of study
{"title":"Comparison of the Nomenclatures of Herbal Substances Used in the Russian and Foreign Pharmacopoeial Texts","authors":"L. N. Frolova, E. L. Kovaleva, E. I. Sakanyan, V. Y. Kuteynikov, V. V. Shelestova, M. A. Cheremisina","doi":"10.30895/1991-2919-2020-10-1-29-40","DOIUrl":"https://doi.org/10.30895/1991-2919-2020-10-1-29-40","url":null,"abstract":". The study of the nomenclature of officinal herbal substances and medicinal plants is important for finding potential ways of expanding the existing range of raw materials used in the production of herbal medicinal products. The authors com-pared the standards included into the State Pharmacopoeia of the Russian Federation, national pharmacopoeias of the Member States of the Eurasian Economic Union, and the world’s leading pharmacopoeias with a focus on herbal substances, medicinal plants, morphological groups of herbal substances, and the proportion of cultivated medicinal plants versus wild medicinal plants. The paper describes historical changes in the nomenclature of herbal substances included in various editions of the Russian Pharmacopoeia. The analysis of the State Register of Medicinal Products revealed the most common morphological groups of herbal substances used in Russia for the production of herbal medicinal products. The paper provides information about the largest Russian manufacturers of herbal medicinal products that preserve national traditions and develop new dosa- ge forms. It outlines ways of improving standardisation of herbal substances using current test methods for characterisation of biologically active substances. The analysis helped to identify potential ways of expanding the range of herbal raw materials: the use of botanical species closely related to officinal ones, increasing the number of morphological groups of substances by inte-grated use of harvested plants, the inclusion of non-officinal botanical species that have a long history of use in the traditional medicine into the Russian list of officinal species. the individual data analysis interpretation of study","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74695276","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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