Pub Date : 2023-05-28DOI: 10.33380/2305-2066-2023-12-2-79-86
N. A. Kovaleva, O. V. Trineeva
Introduction. Scanning electron microscopy is a modern method that allows us to study not only the morphological features of objects, but also to conduct micro-X-ray structural analysis. Currently, the method is being actively introduced into the study of biological objects (including plant ones). Sea buckthorn ( Hippophaë rhamnoides L.) leaves are a non-pharmacopoeial type of medicinal plant raw materials. Further study of the morphology, anatomy and phytochemical composition of leaves can contribute to the production of new, including combined, medicines, which will require the development of a pharmacopoeia article for this medicinal plant raw material. Aim. The aim of the study was to study the morphological and anatomical features of sea buckthorn leaves by scanning electron microscopy. Materials and methods. The object of the study was dried whole leaves of sea buckthorn ( Hippophaë rhamnoides L.), collected in the Voronezh region in 2021 during the period of mass fruit maturity. To carry out the study by scanning electron microscopy, pieces of leaves were previously sprayed with gold on an automatic spraying unit Q150R ES (Quorum Technologies Ltd., United Kingdom) to increase conductivity. Micrographs were obtained using an electron microscope JSM-6510LV (JEOL Ltd., Japan). Results and their discussion. The morphology and some features of the anatomical structure of sea buckthorn leaves were studied and the main microdiagnostic signs (surface character, types of trichomes, the presence of stomata) were clarified. The content of elements (silicon, potassium, aluminum, carbon and calcium) was determined during the microrentgenostructural analysis. Micrographs of pollen grains of the plant were obtained, the presence of the element iron in them was established. Conclusion. For the first time, the method of scanning electron microscopy was used to study the morphological and anatomical features of sea buckthorn leaves. The main diagnostic signs of leaves and their location have been clarified. It has been established that carbon predominates in the composition of the raw material elements, and calcium also accumulates. The accumulation of aluminum, silicon and potassium in numerous hairs densely covering the upper, and especially the lower, surfaces of the leaf blade is assumed. The morphology of the surface of pollen grains of sea buckthorn, having a spherical shape with a spiny shell, has been established. Pollen grains, in addition to carbon, are characterized by the accumulation of iron and silicon.
{"title":"Application of Scanning Electron Microscopy to Study Morphological and Anatomical Features of Sea Buckthorn Leaves","authors":"N. A. Kovaleva, O. V. Trineeva","doi":"10.33380/2305-2066-2023-12-2-79-86","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-79-86","url":null,"abstract":"Introduction. Scanning electron microscopy is a modern method that allows us to study not only the morphological features of objects, but also to conduct micro-X-ray structural analysis. Currently, the method is being actively introduced into the study of biological objects (including plant ones). Sea buckthorn ( Hippophaë rhamnoides L.) leaves are a non-pharmacopoeial type of medicinal plant raw materials. Further study of the morphology, anatomy and phytochemical composition of leaves can contribute to the production of new, including combined, medicines, which will require the development of a pharmacopoeia article for this medicinal plant raw material. Aim. The aim of the study was to study the morphological and anatomical features of sea buckthorn leaves by scanning electron microscopy. Materials and methods. The object of the study was dried whole leaves of sea buckthorn ( Hippophaë rhamnoides L.), collected in the Voronezh region in 2021 during the period of mass fruit maturity. To carry out the study by scanning electron microscopy, pieces of leaves were previously sprayed with gold on an automatic spraying unit Q150R ES (Quorum Technologies Ltd., United Kingdom) to increase conductivity. Micrographs were obtained using an electron microscope JSM-6510LV (JEOL Ltd., Japan). Results and their discussion. The morphology and some features of the anatomical structure of sea buckthorn leaves were studied and the main microdiagnostic signs (surface character, types of trichomes, the presence of stomata) were clarified. The content of elements (silicon, potassium, aluminum, carbon and calcium) was determined during the microrentgenostructural analysis. Micrographs of pollen grains of the plant were obtained, the presence of the element iron in them was established. Conclusion. For the first time, the method of scanning electron microscopy was used to study the morphological and anatomical features of sea buckthorn leaves. The main diagnostic signs of leaves and their location have been clarified. It has been established that carbon predominates in the composition of the raw material elements, and calcium also accumulates. The accumulation of aluminum, silicon and potassium in numerous hairs densely covering the upper, and especially the lower, surfaces of the leaf blade is assumed. The morphology of the surface of pollen grains of sea buckthorn, having a spherical shape with a spiny shell, has been established. Pollen grains, in addition to carbon, are characterized by the accumulation of iron and silicon.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135895202","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 : 2023-05-28DOI: 10.33380/2305-2066-2023-12-2-87-94
Yu. S. Tranova, A. A. Slepnev, I. V. Chernykh, A. V. Shchulkin, P. Yu. Mylnikov, N. M. Popova, M. I. Povetko, E. N. Yakusheva
Introduction. Breast cancer resistance protein (BCRP) is an efflux membrane transporter that controls the pharmacokinetics of a large number of drugs. Its activity may change when taking some endo- and exogenous substances, thus making it a link in drug interactions. Aim. The aim of the study was to develop a method for testing of drugs for belonging to BCRP substrates and inhibitors in vitro. Materials and methods. The work was performed on Caco-2 cells overexpressing BCRP, the cultivation was performed in a transwell-system consisting of the apical and basolateral chambers. Cells were seeded at the bottom of the apical chamber, which is a semipermeable membrane. Primarily, the transport of BCRP substrates: methotrexate, mitoxantrone and quercetin was evaluated in the concentration range of 1, 5, 10, and 50 μM in the direction from the basal chamber to the apical one (Papp b-a) and in the opposite direction (Papp a-b). The ratio Papp b-a / Papp a-b more than «2» characterizes the participation of transporter proteins in the transcellular transport of substances. To confirm the participation of BCRP in their transport the experiment was carried out with the addition of a transporter inhibitor, reserpine, to the transport medium at a concentration of 50 μM. The concentration of substrates in the chambers was analyzed by HPLC-MS/MS. Results and their discussion. The addition of methotrexate (1 μM), mitoxantrone (1 μM), and quercetin (1–10 μM) to both the apical or basolateral chambers of the transwell-system, their content in the recipient chamber was not detected. When methotrexate concentration became 5 μM the Papp b-a / Papp a-b ratio was 3.38 ± 0.08, which indicates the involvement of transporters in its transfer. The addition of methotrexate to the donor chamber at concentrations of 10 and 50 μM, Papp b-a / Papp a-b decreased to values below «2». At mitoxantrone concentration of 5 μM Papp b-a / Papp a-b was 2.72 ± 0.16. An increase in the concentration to 10 μM led to an increase in Papp b-a / Papp a-b to 6.18 ± 0.08. With a substance content of 50 μM the indicator decreased but remained above the value «2». In the quercetin concentration of 50 microns, Papp b-a / Papp was below "2". Reserpine reduced Papp b-a / Papp a-b of methotrexate by 3.31 times ( p = 0.0002), which indicates the elimination of asymmetry in the transport of the substance. At a mitoxantrone concentration of 10 microns, reserpine reduced its Papp b-a / Papp a-b by 3.36 times ( p < 0.0001). The results indicate the participation of BCRP in the control of the transfer of both substances through the cellular monolayer. Conclusion. A method of testing drugs belonging to BCRP substrates and inhibitors using methotrexate (5 μM) and mitoxantrone (10 μM) as marker substrates and reserpine (50 μM) as inhibitor was developed and tested on Caco-2 cells.
介绍。乳腺癌耐药蛋白(Breast cancer resistance protein, BCRP)是一种外排膜转运蛋白，控制着大量药物的药代动力学。它的活性在服用一些内源性和外源性物质时可能发生变化，从而使其成为药物相互作用的一个环节。的目标。本研究的目的是开发一种在体外测试属于BCRP底物和抑制剂的药物的方法。材料和方法。这项工作是在过表达BCRP的Caco-2细胞上进行的，培养是在由顶室和基底侧室组成的transwell系统中进行的。细胞在顶室底部播种，顶室为半透膜。首先，在1、5、10和50 μM的浓度范围内，测定BCRP底物甲氨蝶呤、米托蒽醌和槲皮素在基底室向顶室方向(Papp b-a)和相反方向(Papp a-b)的转运情况。Papp b-a / Papp a-b比值大于“2”表征转运蛋白参与物质的跨细胞转运。为了证实BCRP参与了它们的转运，实验在转运介质中加入了转运抑制剂利血平，浓度为50 μM。采用高效液相色谱-质谱联用(HPLC-MS/MS)分析培养皿中底物的浓度。结果和讨论。将甲氨蝶呤(1 μM)、米托蒽醌(1 μM)和槲皮素(1 ~ 10 μM)分别添加到transwell系统的顶腔和底侧腔中，均未检测其在受体腔中的含量。当甲氨蝶呤浓度为5 μM时，Papp b-a / Papp a-b比值为3.38±0.08，表明转运蛋白参与了其转运。在供体腔中添加浓度为10 μM和50 μM的甲氨蝶呤，Papp b-a / Papp a-b降至«2»以下。在米托蒽醌浓度为5 μM时，Papp b-a / Papp a-b为2.72±0.16。当浓度增加到10 μM时，Papp b-a / Papp a-b增大到6.18±0.08。当物质含量为50 μM时，该指标有所下降，但仍保持在“2”以上。在槲皮素浓度为50 μ m时，Papp b-a / Papp低于“2”。利血平使甲氨蝶呤的Papp b-a / Papp a-b降低了3.31倍(p = 0.0002)，表明消除了物质转运中的不对称性。在米托蒽醌浓度为10微米时，利血平使其pap b-a / pap a-b降低3.36倍(p <0.0001)。结果表明，BCRP参与控制这两种物质通过细胞单层的转移。结论。建立了以甲氨蝶呤(5 μM)和米托蒽醌(10 μM)为标记底物，利血平(50 μM)为抑制剂检测BCRP底物和抑制剂药物的方法，并在Caco-2细胞上进行了实验。
{"title":"Method for Testing of Drugs Belonging to Substrates and Inhibitors of the Transporter Protein BCRP on Caco-2 Cells","authors":"Yu. S. Tranova, A. A. Slepnev, I. V. Chernykh, A. V. Shchulkin, P. Yu. Mylnikov, N. M. Popova, M. I. Povetko, E. N. Yakusheva","doi":"10.33380/2305-2066-2023-12-2-87-94","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-87-94","url":null,"abstract":"Introduction. Breast cancer resistance protein (BCRP) is an efflux membrane transporter that controls the pharmacokinetics of a large number of drugs. Its activity may change when taking some endo- and exogenous substances, thus making it a link in drug interactions. Aim. The aim of the study was to develop a method for testing of drugs for belonging to BCRP substrates and inhibitors in vitro. Materials and methods. The work was performed on Caco-2 cells overexpressing BCRP, the cultivation was performed in a transwell-system consisting of the apical and basolateral chambers. Cells were seeded at the bottom of the apical chamber, which is a semipermeable membrane. Primarily, the transport of BCRP substrates: methotrexate, mitoxantrone and quercetin was evaluated in the concentration range of 1, 5, 10, and 50 μM in the direction from the basal chamber to the apical one (Papp b-a) and in the opposite direction (Papp a-b). The ratio Papp b-a / Papp a-b more than «2» characterizes the participation of transporter proteins in the transcellular transport of substances. To confirm the participation of BCRP in their transport the experiment was carried out with the addition of a transporter inhibitor, reserpine, to the transport medium at a concentration of 50 μM. The concentration of substrates in the chambers was analyzed by HPLC-MS/MS. Results and their discussion. The addition of methotrexate (1 μM), mitoxantrone (1 μM), and quercetin (1–10 μM) to both the apical or basolateral chambers of the transwell-system, their content in the recipient chamber was not detected. When methotrexate concentration became 5 μM the Papp b-a / Papp a-b ratio was 3.38 ± 0.08, which indicates the involvement of transporters in its transfer. The addition of methotrexate to the donor chamber at concentrations of 10 and 50 μM, Papp b-a / Papp a-b decreased to values below «2». At mitoxantrone concentration of 5 μM Papp b-a / Papp a-b was 2.72 ± 0.16. An increase in the concentration to 10 μM led to an increase in Papp b-a / Papp a-b to 6.18 ± 0.08. With a substance content of 50 μM the indicator decreased but remained above the value «2». In the quercetin concentration of 50 microns, Papp b-a / Papp was below \"2\". Reserpine reduced Papp b-a / Papp a-b of methotrexate by 3.31 times ( p = 0.0002), which indicates the elimination of asymmetry in the transport of the substance. At a mitoxantrone concentration of 10 microns, reserpine reduced its Papp b-a / Papp a-b by 3.36 times ( p < 0.0001). The results indicate the participation of BCRP in the control of the transfer of both substances through the cellular monolayer. Conclusion. A method of testing drugs belonging to BCRP substrates and inhibitors using methotrexate (5 μM) and mitoxantrone (10 μM) as marker substrates and reserpine (50 μM) as inhibitor was developed and tested on Caco-2 cells.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"222 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135895201","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 : 2023-05-28DOI: 10.33380/2305-2066-2023-12-2-135-145
T. N. Komarov, P. K. Karnakova, O. A. Archakova, D. S. Shchelgacheva, N. S. Bagaeva, I. E. Shohin, K. Ya. Zaslavskaya, P. A. Bely
Introduction. SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) is expected to remain a persistent global threat. Therefore, development of coronavirus disease 2019 (COVID-19) drugs is the most urgent global issue. Nirmatrelvir and ritonavir combination is an oral antiviral drug combination with activity against SARS-CoV-2. Nirmatrelvir and ritonavir combination is highly efficacious in reducing the risk of COVID-19. The study describes development and validation of high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of nirmatrelvir and ritonavir in human blood plasma. The method could be applied in pharmacokinetic study of nirmatrelvir and ritonavir. Aim. The aim of this study is to develop and validate a HPLC-MS/MS bioanalytical method for the determination of nirmatrelvir and ritonavir in human plasma. Materials and methods. The determination of nirmatrelvir and ritonavir in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: promethazine. Mobile phase: 0.1% formic acid solution in water (Eluent A), 0.1% formic acid in acetonitrile (Eluent B). Column: Phenomenex Luna C18 50 × 2.0 mm, 5 μm. Analytical range: 50.00–10000.00 ng/mL for nirmatrelvir, 5.00–1000.00 ng/mL for ritonavir in human plasma. Ionization source and ionization: electrospray ionization, positive. Detection conditions: 499.90 → 110.10 m/z, 499.90 → 319.20 m/z (nirmatrelvir), 720.90 → 426.00 m/z, 720.90 → 296.20 m/z, 720.90 → 268.10 m/z, 720.90 → 197.10 m/z, 720.90 → 139.90 m/z (ritonavir), 285.15 → 198.05 m/z (promethazine). Results and discussion. This method was validated for selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. Conclusion. The HPLC-MS/MS method for quantitative determination of nirmatrelvir and ritonavir in human plasma was developed and validated. The analytical range was 50.00–10000.00 ng/mL for nirmatrelvir, 5.00–1000.00 ng/mL for ritonavir in human plasma. This method was applied to investigate the pharmacokinetics of nirmatrelvir and ritonavir.
{"title":"Simultaneous Determination of Nirmatrelvir and Ritonavir in Human Plasma by HPLC-MS/MS","authors":"T. N. Komarov, P. K. Karnakova, O. A. Archakova, D. S. Shchelgacheva, N. S. Bagaeva, I. E. Shohin, K. Ya. Zaslavskaya, P. A. Bely","doi":"10.33380/2305-2066-2023-12-2-135-145","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-135-145","url":null,"abstract":"Introduction. SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) is expected to remain a persistent global threat. Therefore, development of coronavirus disease 2019 (COVID-19) drugs is the most urgent global issue. Nirmatrelvir and ritonavir combination is an oral antiviral drug combination with activity against SARS-CoV-2. Nirmatrelvir and ritonavir combination is highly efficacious in reducing the risk of COVID-19. The study describes development and validation of high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of nirmatrelvir and ritonavir in human blood plasma. The method could be applied in pharmacokinetic study of nirmatrelvir and ritonavir. Aim. The aim of this study is to develop and validate a HPLC-MS/MS bioanalytical method for the determination of nirmatrelvir and ritonavir in human plasma. Materials and methods. The determination of nirmatrelvir and ritonavir in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: promethazine. Mobile phase: 0.1% formic acid solution in water (Eluent A), 0.1% formic acid in acetonitrile (Eluent B). Column: Phenomenex Luna C18 50 × 2.0 mm, 5 μm. Analytical range: 50.00–10000.00 ng/mL for nirmatrelvir, 5.00–1000.00 ng/mL for ritonavir in human plasma. Ionization source and ionization: electrospray ionization, positive. Detection conditions: 499.90 → 110.10 m/z, 499.90 → 319.20 m/z (nirmatrelvir), 720.90 → 426.00 m/z, 720.90 → 296.20 m/z, 720.90 → 268.10 m/z, 720.90 → 197.10 m/z, 720.90 → 139.90 m/z (ritonavir), 285.15 → 198.05 m/z (promethazine). Results and discussion. This method was validated for selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. Conclusion. The HPLC-MS/MS method for quantitative determination of nirmatrelvir and ritonavir in human plasma was developed and validated. The analytical range was 50.00–10000.00 ng/mL for nirmatrelvir, 5.00–1000.00 ng/mL for ritonavir in human plasma. This method was applied to investigate the pharmacokinetics of nirmatrelvir and ritonavir.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135895420","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 : 2023-05-28DOI: 10.33380/2305-2066-2023-12-2-104-112
N. A. Dyakova, I. M. Korenskaya, A. I. Slivkin
Introduction. The formation and accumulation of biologically active substances in plants is a complex process associated with a number of environmental factors, including anthropogenic ones. The study of the characteristics of the qualitative composition of essential oil of wormwood grass of bitter different from the ecological point of view of the places of harvesting is relevant. Aim. The aim of this study study of the qualitative composition of essential oil of bitter wormwood grass, harvested in areas of the Voronezh region that are different from an ecological point of view. Materials and methods. In the Voronezh region, 4 points of raw materials procurement were selected, diverse in terms of anthropogenic impact. Isolation of essential oil from the raw materials was carried out according to the method of PS "Wormwood of bitter grass". Component composition of the obtained essential oils was determined using Agilent 7890B GC System (Agilent Technologies, USA) with Agilent 5977A MSD mass selective detector (Agilent Technologies, USA). Data analysis and processing was carried out on the basis of NIST11 databases (from 19.05.2011), MassHunter ver. B.06.00 and NIST MS Search ver. 2.0 software were used. Results and discussion. In a sample of essential oil obtained from reserved raw materials, monoterpene compounds account for more than 82 %, and sesquiterpene compounds – 16.6 %, about 2 % are organic impurities. Intensive biosynthesis of monoterpenes was noted in a sample collected in the area of agricultural fields of the Verkhnekhavsky district, its mass fraction is more than 73 %. In samples of raw materials with anthropogenic load (OJSC "Minudobreniya" and Highway M4), the share of monoterpene compounds is significantly lower (63.7 and 49 %, respectively). The increase in the proportion of sesquiterpene compounds in the last samples of wormwood essential oil may be due to the excessive acidity of the urbanized places of the workpiece. The sesquiterpene compound hamazulene, which stains essential oil blue, is identified in only two samples of gorse grass wormwood harvested along agricultural fields and in M4 tracks, which explains the presence of a blue hue in these oils. Conclusion. The chromato-mass spectrometric analysis of the essential oil of the studied samples of bitter wormwood grass made it possible to identify more than 70 different components in them, while the qualitative composition of the essential oil of the raw materials of different places of the workpiece was significantly different, which may indicate a significant influence of the place of growth of the species and anthropogenic factors on the features of the secondary metabolism of terpene compounds in the plant organism.
{"title":"Comparative Analysis of Quality of Essential Oil of Wormwood Herb Synanthropic Flora of Voronezh Region","authors":"N. A. Dyakova, I. M. Korenskaya, A. I. Slivkin","doi":"10.33380/2305-2066-2023-12-2-104-112","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-104-112","url":null,"abstract":"Introduction. The formation and accumulation of biologically active substances in plants is a complex process associated with a number of environmental factors, including anthropogenic ones. The study of the characteristics of the qualitative composition of essential oil of wormwood grass of bitter different from the ecological point of view of the places of harvesting is relevant. Aim. The aim of this study study of the qualitative composition of essential oil of bitter wormwood grass, harvested in areas of the Voronezh region that are different from an ecological point of view. Materials and methods. In the Voronezh region, 4 points of raw materials procurement were selected, diverse in terms of anthropogenic impact. Isolation of essential oil from the raw materials was carried out according to the method of PS \"Wormwood of bitter grass\". Component composition of the obtained essential oils was determined using Agilent 7890B GC System (Agilent Technologies, USA) with Agilent 5977A MSD mass selective detector (Agilent Technologies, USA). Data analysis and processing was carried out on the basis of NIST11 databases (from 19.05.2011), MassHunter ver. B.06.00 and NIST MS Search ver. 2.0 software were used. Results and discussion. In a sample of essential oil obtained from reserved raw materials, monoterpene compounds account for more than 82 %, and sesquiterpene compounds – 16.6 %, about 2 % are organic impurities. Intensive biosynthesis of monoterpenes was noted in a sample collected in the area of agricultural fields of the Verkhnekhavsky district, its mass fraction is more than 73 %. In samples of raw materials with anthropogenic load (OJSC \"Minudobreniya\" and Highway M4), the share of monoterpene compounds is significantly lower (63.7 and 49 %, respectively). The increase in the proportion of sesquiterpene compounds in the last samples of wormwood essential oil may be due to the excessive acidity of the urbanized places of the workpiece. The sesquiterpene compound hamazulene, which stains essential oil blue, is identified in only two samples of gorse grass wormwood harvested along agricultural fields and in M4 tracks, which explains the presence of a blue hue in these oils. Conclusion. The chromato-mass spectrometric analysis of the essential oil of the studied samples of bitter wormwood grass made it possible to identify more than 70 different components in them, while the qualitative composition of the essential oil of the raw materials of different places of the workpiece was significantly different, which may indicate a significant influence of the place of growth of the species and anthropogenic factors on the features of the secondary metabolism of terpene compounds in the plant organism.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135895203","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 : 2023-05-28DOI: 10.33380/2305-2066-2023-12-2-155-163
I. N. Ampilogova, M. V. Karlina, V. G. Makarov, M. N. Makarova
Introduction. Pharmaceutical development of an innovative highly effective and competitive drug is a long and expensive process, the result of which is quite difficult to predict in advance. To speed up the entry of a new drug to the treatment and reduce the developer's material costs, it is advisable to include preclinical experiments in the process of creating a drug. Text. The purpose of this work is to create a justified approach to the implementation of laboratory pharmaceutical development involving in vivo studies. The inclusion of preclinical studies in the process of laboratory pharmaceutical development will eliminate the negative impact of pharmaceutical factors on the bioavailability of a drugs and avoid errors in the selection of excipients, as well as reduce material and time costs. The review presents examples that demonstrate the relevance of conducting preclinical experiments at different stages of pharmaceutical development. These examples made it possible to describe a clearer algorithm of actions in the laboratory pharmaceutical development of a new drug from the moment a drug candidate molecule is selected. Conclusion. Due to increase the probability of successful pharmaceutical development at initial stage, it is necessary to carry out pharmacokinetic and/or pharmacodynamic experiments to make it possible to develop a drug with an optimal pharmacokinetic profile, reduce the number of preclinical studies, the cost of development, and ensure successful translation of data into clinical practice.
{"title":"The Interconnection Between Pharmaceutical Development and Preclinical Research (Review)","authors":"I. N. Ampilogova, M. V. Karlina, V. G. Makarov, M. N. Makarova","doi":"10.33380/2305-2066-2023-12-2-155-163","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-155-163","url":null,"abstract":"Introduction. Pharmaceutical development of an innovative highly effective and competitive drug is a long and expensive process, the result of which is quite difficult to predict in advance. To speed up the entry of a new drug to the treatment and reduce the developer's material costs, it is advisable to include preclinical experiments in the process of creating a drug. Text. The purpose of this work is to create a justified approach to the implementation of laboratory pharmaceutical development involving in vivo studies. The inclusion of preclinical studies in the process of laboratory pharmaceutical development will eliminate the negative impact of pharmaceutical factors on the bioavailability of a drugs and avoid errors in the selection of excipients, as well as reduce material and time costs. The review presents examples that demonstrate the relevance of conducting preclinical experiments at different stages of pharmaceutical development. These examples made it possible to describe a clearer algorithm of actions in the laboratory pharmaceutical development of a new drug from the moment a drug candidate molecule is selected. Conclusion. Due to increase the probability of successful pharmaceutical development at initial stage, it is necessary to carry out pharmacokinetic and/or pharmacodynamic experiments to make it possible to develop a drug with an optimal pharmacokinetic profile, reduce the number of preclinical studies, the cost of development, and ensure successful translation of data into clinical practice.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135895418","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 : 2023-05-27DOI: 10.33380/2305-2066-2023-12-2-55-60
N. A. Obraztsova, A. A. Samsonov, M. A. Kovtunenko, V. N. Shmeleva, N. A. Golubeva
Introduction. Excipients, impurities contained in them, and sorbed water are one of the reasons for degradation of the active pharmaceutical substance (API). Excipients effect should be especially evaluated for moisture-sensitive APIs. Folic acid (FA) is an important vitamin for humans. It hydrolyze in water under the action of UV irradiation and main decomposition product is N-(p-aminobenzoyl)glutamic acid (impurity A). We found an increase in the content of impurity A during FA film-coated tablets storage in PVC-film and aluminum foil packaging in the absence of UV irradiation. Aim. Investigate the effect of excipients and parameters of the production process on the content of impurity A during storage of FA drugs. Materials and methods. The FA tablets containing 1.0 mg of API produced by direct compression technology were the objects of study. The pressing force (PF) was varied from 5 to 15 kN. Results and discussion. We found that content of impurity A in tablets containing 93.0 % lactose monohydrate and obtained with PF above 10 kN exceeded limit value during storage for 300 days. Probably lactose simultaneously acts both as a source of free water and as a catalyst for FA hydrolysis. Since the interaction of lactose and FA occurs in the solid phase, pressing accelerates hydrolysis by increasing the contact area of substances and the mobility of water molecules. Conclusion. We found that lactose monohydrate probably is the main cause of FA hydrolysis in drugs. Independently of the mechanism of its action, an increase in the PF above 10 kN leads to an increase in the rate of FA hydrolysis. This is due to an increase in the mobility of water molecules and the contact area between the excipient and API. We have selected the optimum pressure range (5–10 kN) for tablet mix containing lactose monohydrate and FA.
{"title":"Influence of Excipients and Pressing Force on the Impurity Content of N-(4-aminobenzoyl)-L-glutamic Acid in Folic Acid Drugs During Storage","authors":"N. A. Obraztsova, A. A. Samsonov, M. A. Kovtunenko, V. N. Shmeleva, N. A. Golubeva","doi":"10.33380/2305-2066-2023-12-2-55-60","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-55-60","url":null,"abstract":"Introduction. Excipients, impurities contained in them, and sorbed water are one of the reasons for degradation of the active pharmaceutical substance (API). Excipients effect should be especially evaluated for moisture-sensitive APIs. Folic acid (FA) is an important vitamin for humans. It hydrolyze in water under the action of UV irradiation and main decomposition product is N-(p-aminobenzoyl)glutamic acid (impurity A). We found an increase in the content of impurity A during FA film-coated tablets storage in PVC-film and aluminum foil packaging in the absence of UV irradiation. Aim. Investigate the effect of excipients and parameters of the production process on the content of impurity A during storage of FA drugs. Materials and methods. The FA tablets containing 1.0 mg of API produced by direct compression technology were the objects of study. The pressing force (PF) was varied from 5 to 15 kN. Results and discussion. We found that content of impurity A in tablets containing 93.0 % lactose monohydrate and obtained with PF above 10 kN exceeded limit value during storage for 300 days. Probably lactose simultaneously acts both as a source of free water and as a catalyst for FA hydrolysis. Since the interaction of lactose and FA occurs in the solid phase, pressing accelerates hydrolysis by increasing the contact area of substances and the mobility of water molecules. Conclusion. We found that lactose monohydrate probably is the main cause of FA hydrolysis in drugs. Independently of the mechanism of its action, an increase in the PF above 10 kN leads to an increase in the rate of FA hydrolysis. This is due to an increase in the mobility of water molecules and the contact area between the excipient and API. We have selected the optimum pressure range (5–10 kN) for tablet mix containing lactose monohydrate and FA.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135949874","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 : 2023-05-27DOI: 10.33380/2305-2066-2023-12-2-21-33
V. N. Aksenova, M. A. Morozova, A. V. Syroeshkin
Introduction. Xanthone glycosides have unique structures and properties. Many efforts focus on the search for C-glycoside derivatives of mangiferin with higher bioavailability. The application of the QSAR approach allows for the optimization of the search for novel xanthone derivatives with the desired characteristics. Aim. Using available descriptors of chemical structure, physical-chemical properties, and biological activity, analyze a sample set of known homologs and analogs of mangiferin to QSAR prognosis bioactivity of new xanthone C-glycosides. Materials and methods. 26 molecules of natural homologs and modified derivatives of mangiferin formed the analyzed sample set. Topological graphs of compounds were constructed using ChemicPen software. ChemicDescript software was used for the calculation of molecular descriptors, including the Balaban index. Physicochemical characteristics of molecules as well as Lipinski's rule criteria were calculated in Molinspiration. The spectrum of the most probable ( P a > 0.7) biological activity of the described compounds were predicted using Pass Online. The software Origin (OriginLab, USA) was used for the graphical representation of the results. Results and discussion. Mangiferin and its natural homologs are the most hydrophilic compounds. The hydrolysis of the C-glycosidic bond, alkylation, acylation, and the introduction of an amino substituent radical into the mangiferin structure led to the increase of its lipophilic properties. The spectrum of the most probable biological activities of the described molecules: antitumor, antioxidant, and cardioprotective effects. The results of ADMET modeling based on the substance-drug similarity criteria showed that only 4 compounds correspond to the rule of five. We proposed the validation model to predict bioactivity from lipophilicity and molecule structure described with Balaban index. The error of prediction obtained in a result of cross-validation turned out to be about less than 3 %. Conclusion. A correlation between the structure and properties of the molecules discussed has been demonstrated. The obtained results can be used for further prediction of the properties of natural and synthetic xanthone C-glycosides and directed synthesis of new active compounds.
介绍。山酮苷具有独特的结构和性质。许多人都在努力寻找具有较高生物利用度的芒果苷c -糖苷衍生物。QSAR方法的应用允许优化搜索具有所需特性的新型山酮衍生物。的目标。利用现有的化学结构、物理化学性质和生物活性描述符，分析了一组已知的芒果苷同源物和类似物对新口山酮c -糖苷QSAR预后生物活性的影响。材料和方法。26个芒果苷的天然同源物和修饰衍生物组成了分析的样品集。使用ChemicPen软件构建化合物的拓扑图。使用ChemicDescript软件计算分子描述符，包括Balaban指数。Molinspiration计算了分子的物理化学特性和利平斯基规则准则。最可能的(P a >0.7)利用Pass Online预测了所述化合物的生物活性。使用Origin软件(OriginLab, USA)对结果进行图形化表示。结果和讨论。芒果苷及其天然同系物是最亲水的化合物。c -糖苷键的水解、烷基化、酰化以及在芒果苷结构中引入氨基取代基导致其亲脂性的增加。描述的分子最可能的生物活性谱:抗肿瘤、抗氧化和心脏保护作用。基于物药相似度标准的ADMET建模结果显示，只有4种化合物符合5规则。我们提出了用Balaban指数描述的亲脂性和分子结构来预测生物活性的验证模型。交叉验证结果的预测误差小于3%。结论。所讨论的分子的结构和性质之间的关系已被证明。所得结果可用于进一步预测天然和合成的克山酮c -糖苷的性质，并指导新的活性化合物的合成。
{"title":"Bioactive Xanthone C-glycoside Derivatives – QSAR Approach","authors":"V. N. Aksenova, M. A. Morozova, A. V. Syroeshkin","doi":"10.33380/2305-2066-2023-12-2-21-33","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-21-33","url":null,"abstract":"Introduction. Xanthone glycosides have unique structures and properties. Many efforts focus on the search for C-glycoside derivatives of mangiferin with higher bioavailability. The application of the QSAR approach allows for the optimization of the search for novel xanthone derivatives with the desired characteristics. Aim. Using available descriptors of chemical structure, physical-chemical properties, and biological activity, analyze a sample set of known homologs and analogs of mangiferin to QSAR prognosis bioactivity of new xanthone C-glycosides. Materials and methods. 26 molecules of natural homologs and modified derivatives of mangiferin formed the analyzed sample set. Topological graphs of compounds were constructed using ChemicPen software. ChemicDescript software was used for the calculation of molecular descriptors, including the Balaban index. Physicochemical characteristics of molecules as well as Lipinski's rule criteria were calculated in Molinspiration. The spectrum of the most probable ( P a > 0.7) biological activity of the described compounds were predicted using Pass Online. The software Origin (OriginLab, USA) was used for the graphical representation of the results. Results and discussion. Mangiferin and its natural homologs are the most hydrophilic compounds. The hydrolysis of the C-glycosidic bond, alkylation, acylation, and the introduction of an amino substituent radical into the mangiferin structure led to the increase of its lipophilic properties. The spectrum of the most probable biological activities of the described molecules: antitumor, antioxidant, and cardioprotective effects. The results of ADMET modeling based on the substance-drug similarity criteria showed that only 4 compounds correspond to the rule of five. We proposed the validation model to predict bioactivity from lipophilicity and molecule structure described with Balaban index. The error of prediction obtained in a result of cross-validation turned out to be about less than 3 %. Conclusion. A correlation between the structure and properties of the molecules discussed has been demonstrated. The obtained results can be used for further prediction of the properties of natural and synthetic xanthone C-glycosides and directed synthesis of new active compounds.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"115 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135949875","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 : 2023-05-27DOI: 10.33380/2305-2066-2023-12-2-34-43
E. A. Dukhnovsky
Introduction. Due to the rapid development of nanotechnology, selenium nanoparticles (NPs) have recently attracted much attention due to their unique physical and chemical properties for biomedical applications, in particular for the treatment of oncological diseases. The review considers the selenium nanoparticles, which are widely studied in the field of oncology. Text. This review is devoted to the analysis of scientific literature on the anticancer activity of selenium nanoparticles against human cancer cell lines, as well as the application of these nanoparticles as a drug delivery system. Besides, the antitumor mechanisms of selenium nanoparticles against malignant neoplasms are discussed. Conclusion. According to the results of literary data analysis, it was found that selenium nanoparticles exhibit a good antitumor effect against various human cancer cell lines. It is shown that the antitumor activity of selenium nanoparticles is mainly related to activation of the extrinsic and intrinsic signaling pathways of apoptosis leading to cancer cell death. Also, selenium nanoparticles are promising systems for delivery of various anticancer drugs, providing high efficiency, bioavailability of drugs in tumor cells and minimizing toxicity to healthy cells.
{"title":"Application of Selenium Nanoparticles in Oncology (Review)","authors":"E. A. Dukhnovsky","doi":"10.33380/2305-2066-2023-12-2-34-43","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-34-43","url":null,"abstract":"Introduction. Due to the rapid development of nanotechnology, selenium nanoparticles (NPs) have recently attracted much attention due to their unique physical and chemical properties for biomedical applications, in particular for the treatment of oncological diseases. The review considers the selenium nanoparticles, which are widely studied in the field of oncology. Text. This review is devoted to the analysis of scientific literature on the anticancer activity of selenium nanoparticles against human cancer cell lines, as well as the application of these nanoparticles as a drug delivery system. Besides, the antitumor mechanisms of selenium nanoparticles against malignant neoplasms are discussed. Conclusion. According to the results of literary data analysis, it was found that selenium nanoparticles exhibit a good antitumor effect against various human cancer cell lines. It is shown that the antitumor activity of selenium nanoparticles is mainly related to activation of the extrinsic and intrinsic signaling pathways of apoptosis leading to cancer cell death. Also, selenium nanoparticles are promising systems for delivery of various anticancer drugs, providing high efficiency, bioavailability of drugs in tumor cells and minimizing toxicity to healthy cells.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135950134","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 : 2023-05-27DOI: 10.33380/2305-2066-2023-12-2-44-54
A. E. Khamitova, D. A. Berillo
Introduction. The search for new, effective and safe pharmacologically active substances remains an urgent task in the field of pharmacy. Many compounds of the piperidine and morpholine series are widely used in medical practice and belong to an important group of biologically active compounds. An informational, literature search on the synthesis of new derivatives of piperidine and morpholine was carried out. The article summarizes the results of studies of new derivatives of piperidine and morpholine as potential sources of biologically active substances. Text. The review is devoted to the relationship between the pharmacological activity of the N-derivatives of piperidine and morpholine in relation to various biological targets and the structure of the substance, the importance of the piperidine and morpholine rings in the design and development of drugs is highlighted. Piperidine and morpholine are considered as prerogative structures not only for increasing activity, but also for obtaining biological substances with desired therapeutic properties and improved pharmacokinetics. Conclusion. The literature review shows the current trend towards the study of morpholine and piperidine derivatives, reveals their high pharmacophore activity. The review will provide researchers with the necessary knowledge base to make chemical structural changes to the structures of drug leaders to enhance pharmacological activities.
{"title":"Overview of Piperidine and Morpholine Derivatives as Promising Sources of Biologically Active Compounds (Review)","authors":"A. E. Khamitova, D. A. Berillo","doi":"10.33380/2305-2066-2023-12-2-44-54","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-44-54","url":null,"abstract":"Introduction. The search for new, effective and safe pharmacologically active substances remains an urgent task in the field of pharmacy. Many compounds of the piperidine and morpholine series are widely used in medical practice and belong to an important group of biologically active compounds. An informational, literature search on the synthesis of new derivatives of piperidine and morpholine was carried out. The article summarizes the results of studies of new derivatives of piperidine and morpholine as potential sources of biologically active substances. Text. The review is devoted to the relationship between the pharmacological activity of the N-derivatives of piperidine and morpholine in relation to various biological targets and the structure of the substance, the importance of the piperidine and morpholine rings in the design and development of drugs is highlighted. Piperidine and morpholine are considered as prerogative structures not only for increasing activity, but also for obtaining biological substances with desired therapeutic properties and improved pharmacokinetics. Conclusion. The literature review shows the current trend towards the study of morpholine and piperidine derivatives, reveals their high pharmacophore activity. The review will provide researchers with the necessary knowledge base to make chemical structural changes to the structures of drug leaders to enhance pharmacological activities.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135950137","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 : 2023-05-27DOI: 10.33380/2305-2066-2023-12-2-62-72
A. M. Poluyanov, A. Kochug, L. S. Mitrofanova, I. D. Nikitin, O. Yu. Vergasov, I. E. Shohin, E. N. Fisher
Introduction. Taurine is a non-proteinogenic amino acid. The molecule is involved in lipid metabolism, adsorbs fat-soluble vitamins, and its conjugates with bile acids contribute to the emulsification of fats in the intestine. Drugs, which include a taurine molecule, have anti-cataract, cardiotonic, metabolic effects, and also stimulate regeneration. Among the dosage forms, where taurine acts as an active substance, there is a solid dosage form – film-coated tablets. One of the methods for assessing the quality of solid dosage forms is a comparative dissolution kinetics test. High-performance chromatography with ultraviolet detection is a widely used method for quantification within the dissolution test, however, for taurine, which does not contain chromophore groups in its structure, this method is not directly applicable. To solve this problem, one can apply the method of pre-column derivatization, because of which an fragment is introduced into the structure, providing a bathochromic shift in the UV spectrum of the starting compound. Aim. Development, validation and approbation analytical method for the quantitative determination of taurine by high-performance chromatography with ultraviolet detection as part of a test comparative kinetics dissolution of taurine tablets with a dosage of 250 and 500 mg. Materials and methods. The following preparations were used for the analysis: taurine tablets, film-coated 250 mg and 500 mg, domestic production with a valid expiration date. The comparative dissolution kinetics test was carried out on a DT 126 Light instrument for the "Dissolution" test (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Nexera-i LC-2040 high-performance liquid chromatograph (Shimadzu Corporation, Japan) equipped with a column and sample thermostat, a degasser, an autosampler, and an ultraviolet detector. Detection was carried out at a wavelength of 254 nm after derivatization of the taurine molecule with 4-toluenesulfonyl chloride. Were used a Shim-pack Velox C18 5 μm 4.6 × 150 mm column (Shimadzu Corporation, Japan) and a Shim-pack Velox C18 EXP Guard Column Cartridge 5 μm 4.6 × 5 mm (Shimadzu Corporation, Japan). Primary data were processed using LabSolutions Single LC software (Shimadzu Corporation, Japan). Results and discussion. The optimal conditions for taurine derivatization have been selected, and a method for the quantitative determination of taurine by HPLC-UV in test comparative kinetics dissolution in three dissolution media: 0.1M hydrochloric acid solution with pH 1.2, acetate buffer solution with pH 4.5, phosphate buffer solution with pH 6.8, as well as in the quality control medium – purified water has been developed and validated. During the validation of the developed methodology, it was found that the validation characteristics are within the acceptance criteria in 4 dissolution media. The analytical range of the method was 0.05–1.2 mg/mL and allows the developed method to b
{"title":"Development, Validation and Approbation Analytical Method for the Quantitative Determination of Taurine by HPLC-UV Method in the Test of Comparative Dissolution Kinetics","authors":"A. M. Poluyanov, A. Kochug, L. S. Mitrofanova, I. D. Nikitin, O. Yu. Vergasov, I. E. Shohin, E. N. Fisher","doi":"10.33380/2305-2066-2023-12-2-62-72","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-62-72","url":null,"abstract":"Introduction. Taurine is a non-proteinogenic amino acid. The molecule is involved in lipid metabolism, adsorbs fat-soluble vitamins, and its conjugates with bile acids contribute to the emulsification of fats in the intestine. Drugs, which include a taurine molecule, have anti-cataract, cardiotonic, metabolic effects, and also stimulate regeneration. Among the dosage forms, where taurine acts as an active substance, there is a solid dosage form – film-coated tablets. One of the methods for assessing the quality of solid dosage forms is a comparative dissolution kinetics test. High-performance chromatography with ultraviolet detection is a widely used method for quantification within the dissolution test, however, for taurine, which does not contain chromophore groups in its structure, this method is not directly applicable. To solve this problem, one can apply the method of pre-column derivatization, because of which an fragment is introduced into the structure, providing a bathochromic shift in the UV spectrum of the starting compound. Aim. Development, validation and approbation analytical method for the quantitative determination of taurine by high-performance chromatography with ultraviolet detection as part of a test comparative kinetics dissolution of taurine tablets with a dosage of 250 and 500 mg. Materials and methods. The following preparations were used for the analysis: taurine tablets, film-coated 250 mg and 500 mg, domestic production with a valid expiration date. The comparative dissolution kinetics test was carried out on a DT 126 Light instrument for the \"Dissolution\" test (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Nexera-i LC-2040 high-performance liquid chromatograph (Shimadzu Corporation, Japan) equipped with a column and sample thermostat, a degasser, an autosampler, and an ultraviolet detector. Detection was carried out at a wavelength of 254 nm after derivatization of the taurine molecule with 4-toluenesulfonyl chloride. Were used a Shim-pack Velox C18 5 μm 4.6 × 150 mm column (Shimadzu Corporation, Japan) and a Shim-pack Velox C18 EXP Guard Column Cartridge 5 μm 4.6 × 5 mm (Shimadzu Corporation, Japan). Primary data were processed using LabSolutions Single LC software (Shimadzu Corporation, Japan). Results and discussion. The optimal conditions for taurine derivatization have been selected, and a method for the quantitative determination of taurine by HPLC-UV in test comparative kinetics dissolution in three dissolution media: 0.1M hydrochloric acid solution with pH 1.2, acetate buffer solution with pH 4.5, phosphate buffer solution with pH 6.8, as well as in the quality control medium – purified water has been developed and validated. During the validation of the developed methodology, it was found that the validation characteristics are within the acceptance criteria in 4 dissolution media. The analytical range of the method was 0.05–1.2 mg/mL and allows the developed method to b","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135950135","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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