Background: This study investigates the application of polyamidoamine (PAMAM) dendrimers as an innovative drug delivery approach for enhancing the pharmacokinetic profile of ursolic acid (UA), a pentacyclic triterpenoid with multifaceted therapeutic properties. UA, sourced from plants like Sanguisorba officinalis and Salvia officinalis, has been extensively studied for its pharmacological characteristics, including anti-inflammatory, antioxidant, and anti-diabetic properties, as recognized in Traditional Chinese Medicine (TCM). The clinical utility of UA is hampered by low bioavailability, which is attributed to its hydrophobic nature. To address this limitation, we explore the use of PAMAM dendrimers, known for their drug delivery potential. Methods: The UA-PAMAM G0 dendrimers were synthesized with varying molar ratios. Characterization included size analysis, PDI, and zeta potential determination. FTIR confirmed the chemical structure. Male Wistar rats were acclimatized and administered UA control suspension and UA-G0 dendrimer complex orally. Blood samples were collected for pharmacokinetic analysis. The study obtained IAEC approval. Results: The UA-PAMAM G0 dendrimer complexes exhibited varying sizes based on molar ratios, with the 2:1 ratio showing significantly smaller dimensions. FTIR confirmed successful conjugation. In the pharmacokinetic study, the UA-G0 dendrimer complex demonstrated higher plasma concentrations than UA alone, as indicated by increased Cmax and AUC values. The results suggest enhanced oral delivery and bioavailability of UA in the dendrimer complex. Conclusion: This study demonstrated the successful synthesis of UA-PAMAM G0 dendrimer complexes with size variations based on molar ratios. The pharmacokinetic analysis revealed improved plasma concentrations and bioavailability of UA in the dendrimer complex compared to UA alone. These findings highlight the potential of PAMAM dendrimers for enhancing the oral delivery of hydrophobic compounds like UA, bridging the gap between traditional herbal medicine and modern drug delivery strategies. Further research can explore the broader applications of such dendrimer complexes in drug delivery systems.
背景：本研究调查了聚酰胺胺（PAMAM）树枝状聚合物作为一种创新的给药方法在增强熊果酸（UA）药代动力学特征方面的应用。熊果酸来源于三七和丹参等植物，其药理特性已得到广泛研究，包括抗炎、抗氧化和抗糖尿病特性，这一点已得到传统中医的认可。尿囊素的疏水性导致其生物利用率较低，从而影响了其临床应用。为解决这一局限性，我们探索了 PAMAM 树枝状聚合物的使用方法，众所周知，PAMAM 树枝状聚合物具有药物输送潜力。方法：以不同的摩尔比合成了 UA-PAMAM G0 树枝状聚合物。表征包括尺寸分析、PDI 和 zeta 电位测定。傅立叶变换红外光谱确认了化学结构。雄性 Wistar 大鼠适应环境后，口服 UA 对照悬浮液和 UA-G0 树枝状聚合物复合物。收集血液样本用于药代动力学分析。该研究已获得 IAEC 批准。研究结果根据摩尔比，UA-PAMAM G0 树枝状聚合物复合物显示出不同的尺寸，其中 2:1 比率的尺寸明显较小。傅立叶变换红外光谱证实共轭成功。在药代动力学研究中，UA-G0 树枝状聚合物复合物的血浆浓度高于单独的 UA，表现为 Cmax 值和 AUC 值增加。结果表明，树枝状聚合物复合物提高了尿酸的口服给药和生物利用度。结论本研究成功合成了 UA-PAMAM G0 树枝状聚合物复合物，并根据摩尔比进行了尺寸变化。药代动力学分析表明，与单独使用 UA 相比，树枝状聚合物复合物中 UA 的血浆浓度和生物利用度均有所提高。这些发现凸显了 PAMAM 树枝状聚合物在增强 UA 等疏水性化合物口服给药方面的潜力，弥补了传统中药与现代给药策略之间的差距。进一步的研究可以探索此类树枝状聚合物复合物在给药系统中的更广泛应用。
{"title":"Pharmacokinetic Assessments of Ursolic Loaded-Dendrimer Complex","authors":"Aditya Singh, Vaseem Ahamad Ansari, Tarique Mahmood Ansari, Rufaida Wasim, Juber Akhtar, Shubhrat Maheshwari","doi":"10.2174/0115734129300077240813063934","DOIUrl":"https://doi.org/10.2174/0115734129300077240813063934","url":null,"abstract":"Background: This study investigates the application of polyamidoamine (PAMAM) dendrimers as an innovative drug delivery approach for enhancing the pharmacokinetic profile of ursolic acid (UA), a pentacyclic triterpenoid with multifaceted therapeutic properties. UA, sourced from plants like Sanguisorba officinalis and Salvia officinalis, has been extensively studied for its pharmacological characteristics, including anti-inflammatory, antioxidant, and anti-diabetic properties, as recognized in Traditional Chinese Medicine (TCM). The clinical utility of UA is hampered by low bioavailability, which is attributed to its hydrophobic nature. To address this limitation, we explore the use of PAMAM dendrimers, known for their drug delivery potential. Methods: The UA-PAMAM G0 dendrimers were synthesized with varying molar ratios. Characterization included size analysis, PDI, and zeta potential determination. FTIR confirmed the chemical structure. Male Wistar rats were acclimatized and administered UA control suspension and UA-G0 dendrimer complex orally. Blood samples were collected for pharmacokinetic analysis. The study obtained IAEC approval. Results: The UA-PAMAM G0 dendrimer complexes exhibited varying sizes based on molar ratios, with the 2:1 ratio showing significantly smaller dimensions. FTIR confirmed successful conjugation. In the pharmacokinetic study, the UA-G0 dendrimer complex demonstrated higher plasma concentrations than UA alone, as indicated by increased Cmax and AUC values. The results suggest enhanced oral delivery and bioavailability of UA in the dendrimer complex. Conclusion: This study demonstrated the successful synthesis of UA-PAMAM G0 dendrimer complexes with size variations based on molar ratios. The pharmacokinetic analysis revealed improved plasma concentrations and bioavailability of UA in the dendrimer complex compared to UA alone. These findings highlight the potential of PAMAM dendrimers for enhancing the oral delivery of hydrophobic compounds like UA, bridging the gap between traditional herbal medicine and modern drug delivery strategies. Further research can explore the broader applications of such dendrimer complexes in drug delivery systems.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"4312 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.2174/0115734129330671240812063919
Muzammil Husain, Yogeeta O. Agrawal
Introduction/Objective: The current study examines the methodical Quality by Design (QbD) that facilitated the creation of an easy-to-use, quick, affordable, and stability-indicating reversed- phase high-performance liquid chromatography (RP-HPLC) technique for the efficient analysis of aloe-emodin. Methods: The chromatographic conditions were optimized with the Design Expert software 11.0 version, i.e., flow rate, buffer concentration, and column temperature. Results: The results of the linearity graph show R2 = 0.9988. The LOQ was 0.07949 μg/mL and the LOD was 0.02623 μg/mL. According to ICH rules, the technique validation parameters were within the allowed range. Utilizing the Design Expert 11.0 version, the Box–Behnken design experimental design explains the relationships between flow rate, buffer concentration, and column temperature at three distinct levels. The responses were monitored: the retention time (Rt), tailing factor (Tf), and number of theoretical plates (NTPs). Conclusion: The suggested approach was appropriate for quantitative determination and may be used in clinical pharmacokinetic investigations, biopharmaceutics, accredited testing laboratories, and quality control departments in enterprises.
{"title":"Quality by Design Approach for the Development and Validation of a Robust RP-HPLC Method for the Estimation of Aloe-Emodin","authors":"Muzammil Husain, Yogeeta O. Agrawal","doi":"10.2174/0115734129330671240812063919","DOIUrl":"https://doi.org/10.2174/0115734129330671240812063919","url":null,"abstract":"Introduction/Objective: The current study examines the methodical Quality by Design (QbD) that facilitated the creation of an easy-to-use, quick, affordable, and stability-indicating reversed- phase high-performance liquid chromatography (RP-HPLC) technique for the efficient analysis of aloe-emodin. Methods: The chromatographic conditions were optimized with the Design Expert software 11.0 version, i.e., flow rate, buffer concentration, and column temperature. Results: The results of the linearity graph show R2 = 0.9988. The LOQ was 0.07949 μg/mL and the LOD was 0.02623 μg/mL. According to ICH rules, the technique validation parameters were within the allowed range. Utilizing the Design Expert 11.0 version, the Box–Behnken design experimental design explains the relationships between flow rate, buffer concentration, and column temperature at three distinct levels. The responses were monitored: the retention time (Rt), tailing factor (Tf), and number of theoretical plates (NTPs). Conclusion: The suggested approach was appropriate for quantitative determination and may be used in clinical pharmacokinetic investigations, biopharmaceutics, accredited testing laboratories, and quality control departments in enterprises.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"32 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Favipiravir is an antiviral drug having pyrazine group moiety. It is a reliable and an efficient green solvent, and a highly recoverable bio-sampling method is required for it. It is widely used in COVID-19 treatment for the prevention of the spread of viral infections in the body Objective: This proposed green solvent (ionic liquid)-based bioassay study aimed to quantify favipiravir in rat-dried blood spots using Dispersive Liquid-liquid Microextraction (IL-DLLME). Methods: The proposed bioassay separation was achieved through an isocratic elution mode using a hybrid silica-based ODS column (250 × 4.6 mm; 5 μm), a column temperature of 25°C, an injection volume of 10 μL, a flow rate of 1.0 mL/min, and a detector wavelength set at 310 nm. The run time was less than 10 minutes. Mobile phase was delivered with acetonitrile, methanol, and 10 mM Na2HPO4 at pH 4.0 ± 0.5, (15: 20: 65, v/v/v). In a microtube, 50 mL of Ionic Liquid (IL), 500 μL of disperser ACN, 50 μL of 10% NaCl, and IS (20 ng mL-1) were added to perform the Dried Blood Spot (DBS) sample extraction methodology. The advantages of the proposed methodology have been found to include minimum hematocrit effect and an adequate blood volume for testing, easy transportation, and significant extraction recovery. The sample analysis has been carried out using HPLC-PDA with oseltamivir used as an internal standard. Results: We have investigated the important variables, i.e., salt concentration (10% NaCl, analyte recovery being higher) and disperser solvent [50μL of BMIHP plus 500 μL of ACN (v/v) yielding the highest recovery], in the extraction process. Extraction Recovery (ER) and Enrichment Factor (EF) were also evaluated using the IL-DLLME method. The calibration curve examined a range of 0.5-150 μg/mL, with a lower Limit of Quantification (LOQ) being 0.5 μg/mL in QC as well as calibration samples, respectively. Conclusion: Significant bioanalytical validation has been performed and all the parameters have been evaluated systematically as per bioanalytical method validation protocols, i.e., US FDA- 2018 guidelines. The following analytical parameters have been covered: standard curve, limit of quantification, range, recovery, stability, accuracy, precision, sensitivity, ER, EF, and selectivity. The developed bioassay method has been successfully applied in the pharmacokinetic studies of rats and successfully applied in bulk drugs.
{"title":"Efficient Green Solvent Extraction and Bioassay Studies of Favipiravir in Rat Dried Blood Spots Using Ionic Liquid-Based Dispersive Liquid-Liquid Microextraction (IL-DLLME) Coupled with HPLC-PDA: Application to Bioequivalence Studies","authors":"Kasturi Rajasekhar, Challa Gangu Naidu, Chebolu Naga Sesha Sai Pavan Kumar, Bondigalla Ramachnadra","doi":"10.2174/0115734129296648240812111928","DOIUrl":"https://doi.org/10.2174/0115734129296648240812111928","url":null,"abstract":"Background: Favipiravir is an antiviral drug having pyrazine group moiety. It is a reliable and an efficient green solvent, and a highly recoverable bio-sampling method is required for it. It is widely used in COVID-19 treatment for the prevention of the spread of viral infections in the body Objective: This proposed green solvent (ionic liquid)-based bioassay study aimed to quantify favipiravir in rat-dried blood spots using Dispersive Liquid-liquid Microextraction (IL-DLLME). Methods: The proposed bioassay separation was achieved through an isocratic elution mode using a hybrid silica-based ODS column (250 × 4.6 mm; 5 μm), a column temperature of 25°C, an injection volume of 10 μL, a flow rate of 1.0 mL/min, and a detector wavelength set at 310 nm. The run time was less than 10 minutes. Mobile phase was delivered with acetonitrile, methanol, and 10 mM Na2HPO4 at pH 4.0 ± 0.5, (15: 20: 65, v/v/v). In a microtube, 50 mL of Ionic Liquid (IL), 500 μL of disperser ACN, 50 μL of 10% NaCl, and IS (20 ng mL-1) were added to perform the Dried Blood Spot (DBS) sample extraction methodology. The advantages of the proposed methodology have been found to include minimum hematocrit effect and an adequate blood volume for testing, easy transportation, and significant extraction recovery. The sample analysis has been carried out using HPLC-PDA with oseltamivir used as an internal standard. Results: We have investigated the important variables, i.e., salt concentration (10% NaCl, analyte recovery being higher) and disperser solvent [50μL of BMIHP plus 500 μL of ACN (v/v) yielding the highest recovery], in the extraction process. Extraction Recovery (ER) and Enrichment Factor (EF) were also evaluated using the IL-DLLME method. The calibration curve examined a range of 0.5-150 μg/mL, with a lower Limit of Quantification (LOQ) being 0.5 μg/mL in QC as well as calibration samples, respectively. Conclusion: Significant bioanalytical validation has been performed and all the parameters have been evaluated systematically as per bioanalytical method validation protocols, i.e., US FDA- 2018 guidelines. The following analytical parameters have been covered: standard curve, limit of quantification, range, recovery, stability, accuracy, precision, sensitivity, ER, EF, and selectivity. The developed bioassay method has been successfully applied in the pharmacokinetic studies of rats and successfully applied in bulk drugs.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"65 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.2174/0115734129306621240813074201
Liping Xie, Zhen’an Wu, Na Wei, Liang Zhang, Jiajian Tang, Hongmei Wang
Purpose: This paper aims to analyze the clinical distribution and drug resistance changes of Klebsiella Pneumoniae (KPN) from 2017 to 2021 in the Beijing Hospital of Integrated Traditional Chinese and Western Medicine to provide a reference for the clinical rational use of antibiotics. Methods: We collected Klebsiella Pneumoniae isolated from various clinical specimens in 2017-2021, analyzed the isolation rate, specimen distribution, and department distribution characteristics during the five years, and statistically analyzed their drug sensitivity tests and multiple drug resistance. Zhuhai Deere DL-96 full-automatic microbial analyzer was used for bacterial identification and drug sensitivity tests. The drug sensitivity test was interpreted according to the standards recommended by the American Clinical and Laboratory Standards Institute (CLSI). Results: A total of 1057 strains of Klebsiella Pneumoniae were identified between 2017 and 2021, with proportions of 18.6%, 15.7%, 15.4%, 15.1%, and 15.0% in each respective year. Specimen distribution included sputum (66.0%), urine (17.9%), throat swab (9.4%), secretion (2.4%), pus (0.7%), venous blood (0.6%), vaginal swab (0.4%), and other sources (2.6%). Distribution by the department revealed specimens originating from the respiratory department (21.2%), cardiology department (17.8%), neurology department (13.4%), oncology department (13.0%), nephrology department (12.2%), acupuncture department (10.1%), and other departments (12.3%). In terms of drug susceptibility testing, Klebsiella Pneumoniae exhibited high resistance rates to ceftriaxone, cefotaxime, ceftazidime, and ampicillin/sulbactam, with rates of 50.8%, 46.8%, 46.3%, and 43.6% respectively. Conversely, resistance rates to minocycline, amikacin, imipenem, and meropenem were relatively low, at 8.6%, 16.5%, 8.5%, and 9.4% respectively. Resistance rates to cefepime/- sulbactam and piperacillin/tazobactam were 29.9% and 28.9%, respectively, while cephalosporin resistance rates ranged from 36.1% to 50.8%. Regarding multidrug resistance, the detection rates of ESBL-producing Klebsiella Pneumoniae were 8.2%, 10.9%, 4.5%, 10.6%, and 6.4% from 2017 to 2021, with an average detection rate of 7.9%. The detection rates of CR-Kp were 12.1%, 11.7%, 5.8%, 9.9%, and 8.9% respectively, averaging 9.6% over the five-year period. Conclusion: The sputum specimen of Klebsiella Pneumoniae exhibits the highest detection rate among specimen distributions, signifying its significance as a pathogenic bacterium in respiratory tract infections. Notably, the respiratory department demonstrates the highest detection rate, underscoring the necessity to enhance the monitoring and management of Klebsiella Pneumoniae infections in respiratory patients. Over the past five years, our hospital has observed a decreasing trend in the overall drug resistance rate of Klebsiella Pneumoniae to 17 antibiotics. While imipenem and meropenem exhibit minimal resistance rates, these carbap
{"title":"Evaluation of Clinical Distribution and Antimicrobial Resistance of Klebsiella Pneumoniae","authors":"Liping Xie, Zhen’an Wu, Na Wei, Liang Zhang, Jiajian Tang, Hongmei Wang","doi":"10.2174/0115734129306621240813074201","DOIUrl":"https://doi.org/10.2174/0115734129306621240813074201","url":null,"abstract":"Purpose: This paper aims to analyze the clinical distribution and drug resistance changes of Klebsiella Pneumoniae (KPN) from 2017 to 2021 in the Beijing Hospital of Integrated Traditional Chinese and Western Medicine to provide a reference for the clinical rational use of antibiotics. Methods: We collected Klebsiella Pneumoniae isolated from various clinical specimens in 2017-2021, analyzed the isolation rate, specimen distribution, and department distribution characteristics during the five years, and statistically analyzed their drug sensitivity tests and multiple drug resistance. Zhuhai Deere DL-96 full-automatic microbial analyzer was used for bacterial identification and drug sensitivity tests. The drug sensitivity test was interpreted according to the standards recommended by the American Clinical and Laboratory Standards Institute (CLSI). Results: A total of 1057 strains of Klebsiella Pneumoniae were identified between 2017 and 2021, with proportions of 18.6%, 15.7%, 15.4%, 15.1%, and 15.0% in each respective year. Specimen distribution included sputum (66.0%), urine (17.9%), throat swab (9.4%), secretion (2.4%), pus (0.7%), venous blood (0.6%), vaginal swab (0.4%), and other sources (2.6%). Distribution by the department revealed specimens originating from the respiratory department (21.2%), cardiology department (17.8%), neurology department (13.4%), oncology department (13.0%), nephrology department (12.2%), acupuncture department (10.1%), and other departments (12.3%). In terms of drug susceptibility testing, Klebsiella Pneumoniae exhibited high resistance rates to ceftriaxone, cefotaxime, ceftazidime, and ampicillin/sulbactam, with rates of 50.8%, 46.8%, 46.3%, and 43.6% respectively. Conversely, resistance rates to minocycline, amikacin, imipenem, and meropenem were relatively low, at 8.6%, 16.5%, 8.5%, and 9.4% respectively. Resistance rates to cefepime/- sulbactam and piperacillin/tazobactam were 29.9% and 28.9%, respectively, while cephalosporin resistance rates ranged from 36.1% to 50.8%. Regarding multidrug resistance, the detection rates of ESBL-producing Klebsiella Pneumoniae were 8.2%, 10.9%, 4.5%, 10.6%, and 6.4% from 2017 to 2021, with an average detection rate of 7.9%. The detection rates of CR-Kp were 12.1%, 11.7%, 5.8%, 9.9%, and 8.9% respectively, averaging 9.6% over the five-year period. Conclusion: The sputum specimen of Klebsiella Pneumoniae exhibits the highest detection rate among specimen distributions, signifying its significance as a pathogenic bacterium in respiratory tract infections. Notably, the respiratory department demonstrates the highest detection rate, underscoring the necessity to enhance the monitoring and management of Klebsiella Pneumoniae infections in respiratory patients. Over the past five years, our hospital has observed a decreasing trend in the overall drug resistance rate of Klebsiella Pneumoniae to 17 antibiotics. While imipenem and meropenem exhibit minimal resistance rates, these carbap","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.2174/0115734129310868240805065851
Senem Şanlı, Mustafa Sinan Kaynak, Nurullah Sanli, Emine Ertürk Balta
Introduction: Antiretroviral medications are widely used to treat HIV infections. Lamivudine (3TC) is prescribed for HIV-1 infection management in adults and pediatrics, while valganciclovir (VGC) is a prodrug of ganciclovir derived from valine. Method: The Biopharmaceutics Classification System (BCS) estimates the contributions of intestinal permeability, dissolution, and solubility in oral drug absorption. Intestinal permeability refers to a substance's capacity to pass through the protective layer of cells in the intestine. The intestinal permeability of 3TC and VGC was analyzed and categorized using the single-pass intestinal perfusion technique according to the BCS in male Sprague Dawley rats, and a reversed- phase HPLC method was validated for precise and accurate measurement. objective: Intestinal permeability refers to a substance's capacity to pass through the protective layer of cells in the intestine. Result: According to the BCS, 3TC and VGC have been classified as having low permeability when compared to metoprolol tartrate, which is classified as Class I with good permeability and resolution. Conclusion: The permeability values derived from this work can be valuable in exposure assessment models.
{"title":"Investigation of the Permeability of Antiretroviral Drugs Lamivudine and Valganciclovir via Single-Pass Intestinal Perfusion (SPIP) Method","authors":"Senem Şanlı, Mustafa Sinan Kaynak, Nurullah Sanli, Emine Ertürk Balta","doi":"10.2174/0115734129310868240805065851","DOIUrl":"https://doi.org/10.2174/0115734129310868240805065851","url":null,"abstract":"Introduction: Antiretroviral medications are widely used to treat HIV infections. Lamivudine (3TC) is prescribed for HIV-1 infection management in adults and pediatrics, while valganciclovir (VGC) is a prodrug of ganciclovir derived from valine. Method: The Biopharmaceutics Classification System (BCS) estimates the contributions of intestinal permeability, dissolution, and solubility in oral drug absorption. Intestinal permeability refers to a substance's capacity to pass through the protective layer of cells in the intestine. The intestinal permeability of 3TC and VGC was analyzed and categorized using the single-pass intestinal perfusion technique according to the BCS in male Sprague Dawley rats, and a reversed- phase HPLC method was validated for precise and accurate measurement. objective: Intestinal permeability refers to a substance's capacity to pass through the protective layer of cells in the intestine. Result: According to the BCS, 3TC and VGC have been classified as having low permeability when compared to metoprolol tartrate, which is classified as Class I with good permeability and resolution. Conclusion: The permeability values derived from this work can be valuable in exposure assessment models.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"18 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16DOI: 10.2174/0115734129317614240809053901
Mohammad Alwahsh, Hamzeh Abumansour, Arwa R. Althaher, Roland Hergenröder
: Individual physiological and pathophysiological states, as well as the environment, impact the metabolome. With the help of metabolomics, clinical investigations can better understand the mechanisms underlying disease. The expansion of analytical techniques intended to examine biofluids thoroughly facilitates the characterization of numerous illness biomarkers. Metabolomics aims to identify subtle variances in metabolic profiles among biological systems in different physiological or pathological conditions. In our review, we start by outlining the seven objectives of metabolic profile analysis, which range from creating a data table to integrating multiple omics for systems biology. Then, approaches to data reduction and deconvolution, normalization, scaling, and data transformations are provided. These techniques for preprocessing and pretreatment cover a variety of topics.
{"title":"Metabolic Profiling Techniques and Their Application in Cancer Research","authors":"Mohammad Alwahsh, Hamzeh Abumansour, Arwa R. Althaher, Roland Hergenröder","doi":"10.2174/0115734129317614240809053901","DOIUrl":"https://doi.org/10.2174/0115734129317614240809053901","url":null,"abstract":": Individual physiological and pathophysiological states, as well as the environment, impact the metabolome. With the help of metabolomics, clinical investigations can better understand the mechanisms underlying disease. The expansion of analytical techniques intended to examine biofluids thoroughly facilitates the characterization of numerous illness biomarkers. Metabolomics aims to identify subtle variances in metabolic profiles among biological systems in different physiological or pathological conditions. In our review, we start by outlining the seven objectives of metabolic profile analysis, which range from creating a data table to integrating multiple omics for systems biology. Then, approaches to data reduction and deconvolution, normalization, scaling, and data transformations are provided. These techniques for preprocessing and pretreatment cover a variety of topics.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"54 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16DOI: 10.2174/0115734129298520240812062841
Yanxin Dang, Menghan Du, Xiuxiu Sun, Zeqi Sun, Jie Liu, Minzhen Xie, Zhouxiu Chen, Siqi Gu, Qi Wang, Guijun Liu
Context: Potentilla discolor Bge. is a plant extensively utilized in Traditional Chinese Medicine (TCMs). Nevertheless, our knowledge of the chemical components and metabolic complexities in its extracts is still quite limited. Objective: The study aimed to thoroughly analyze the flavonoid metabolism in Potentilla discolor Bge. extracts and conduct a pharmacodynamic evaluation. Methods: In this study, we investigated the metabolism of flavonoids in Potentilla discolor Bge. extracts using SD rats. The research adopted the strategy of “in vivo metabolism assessment, basic study of pharmacodynamics and preliminary evaluation of molecular docking” to systematically investigate the pharmacodynamic substances and targets of action of Potentilla discolor Bge.. Results: The results of the study showed that the main metabolic forms of Potentilla discolor Bge. in vivo include hydroxylation, methylation, and glycosylation. Among them, luteolin in the total flavonoids of Potentilla discolor Bge. has the strongest antimicrobial and antioxidant ability. Outcomes of molecular docking experiments indicated that the glycosylated metabolite of luteolin had a significant advantage in acting with Glp-1 (Glucagon-like peptide-1). Conclusion: The present study revealed the metabolic pathways of total flavonoids in Potentilla discolor Bge. It not only effectively screened out their pharmacodynamic substances and targets but also provided a theoretical basis for the application of TCMs into a systematic application and also provided ideas for the direction of drug optimization in the future. However, the sample range of this study is limited, and it generalizability needs to be investigated.
{"title":"Analyzing the Metabolic Destiny of Potentilla discolor Bge. Extract and Its Primary Components in Rat Models","authors":"Yanxin Dang, Menghan Du, Xiuxiu Sun, Zeqi Sun, Jie Liu, Minzhen Xie, Zhouxiu Chen, Siqi Gu, Qi Wang, Guijun Liu","doi":"10.2174/0115734129298520240812062841","DOIUrl":"https://doi.org/10.2174/0115734129298520240812062841","url":null,"abstract":"Context: Potentilla discolor Bge. is a plant extensively utilized in Traditional Chinese Medicine (TCMs). Nevertheless, our knowledge of the chemical components and metabolic complexities in its extracts is still quite limited. Objective: The study aimed to thoroughly analyze the flavonoid metabolism in Potentilla discolor Bge. extracts and conduct a pharmacodynamic evaluation. Methods: In this study, we investigated the metabolism of flavonoids in Potentilla discolor Bge. extracts using SD rats. The research adopted the strategy of “in vivo metabolism assessment, basic study of pharmacodynamics and preliminary evaluation of molecular docking” to systematically investigate the pharmacodynamic substances and targets of action of Potentilla discolor Bge.. Results: The results of the study showed that the main metabolic forms of Potentilla discolor Bge. in vivo include hydroxylation, methylation, and glycosylation. Among them, luteolin in the total flavonoids of Potentilla discolor Bge. has the strongest antimicrobial and antioxidant ability. Outcomes of molecular docking experiments indicated that the glycosylated metabolite of luteolin had a significant advantage in acting with Glp-1 (Glucagon-like peptide-1). Conclusion: The present study revealed the metabolic pathways of total flavonoids in Potentilla discolor Bge. It not only effectively screened out their pharmacodynamic substances and targets but also provided a theoretical basis for the application of TCMs into a systematic application and also provided ideas for the direction of drug optimization in the future. However, the sample range of this study is limited, and it generalizability needs to be investigated.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Preservatives called parabens are frequently found in medicinal formulations and personal hygiene products. However, questions have been raised concerning their possible impact on health, leading to the need for reliable methods to determine their presence and degradation of products. Objective: This study aimed to create and validate a straightforward, accurate, dependable, and selective method for determining the levels of methyl and propyl parabens, as well as the breakdown product p-hydroxy benzoic acid. Additionally, a force degradation study was conducted to assess the stability of parabens in a parenteral formulation under various conditions. Method: Separation of the compounds was achieved using X-Bridge C18 (250 X 4.6 mm) 5μm column with a mobile phase composed of water (pH 3.0 with glacial acetic acid) and methanol (30:70). Detection was carried out at 254 nm using a UV detector with an injection volume of 20 μL and a flow rate of 1.0 mL/min. Force degradation studies included acid, base, oxidation, thermal, and photo-degradation. Results: Under the described conditions, the separation of p-hydroxy benzoic acid, methylparaben, and propylparaben was achieved in less than 12.0 minutes. The concentration ranges for p-hydroxy benzoic acid, methylparaben, and propylparaben were determined to be 1ng - 50 μg/mL, 100ng - 50μg/mL, and 100ng -12μ g/mL, respectively. The linearity, accuracy, and precision of the method were within acceptable ranges. Discussion: Maximum degradation of methylparaben was observed under base and neutral conditions in the first sample and under base and thermal conditions in the second sample. Similarly, maximum degradation of propylparaben was observed under base conditions in the first sample and under neutral and thermal conditions in the second sample. P-hydroxy benzoic acid degradation was observed under all conditions, with the highest degradation occurring in 0.1 N NaOH and 0.1 N HCl at 60°C. Conclusion: The developed method proved to be effective for the determination of methyl and propylparaben, along with their degradation product p-hydroxy benzoic acid, in pharmaceutical formulations. The results of the force degradation study provided valuable insights into the stability of parabens under various conditions, highlighting the importance of monitoring and controlling their degradation in pharmaceutical products.
{"title":"Analyzing Paraben Degradation in Parenteral Formulations with High-Performance Liquid Chromatography","authors":"Lalit Singh, Shefali Mehla, Vishnu Mittal, Girish Chandra Arya, Anjali Sharma, Devkant Sharma","doi":"10.2174/0115734129319225240812055549","DOIUrl":"https://doi.org/10.2174/0115734129319225240812055549","url":null,"abstract":"Background: Preservatives called parabens are frequently found in medicinal formulations and personal hygiene products. However, questions have been raised concerning their possible impact on health, leading to the need for reliable methods to determine their presence and degradation of products. Objective: This study aimed to create and validate a straightforward, accurate, dependable, and selective method for determining the levels of methyl and propyl parabens, as well as the breakdown product p-hydroxy benzoic acid. Additionally, a force degradation study was conducted to assess the stability of parabens in a parenteral formulation under various conditions. Method: Separation of the compounds was achieved using X-Bridge C18 (250 X 4.6 mm) 5μm column with a mobile phase composed of water (pH 3.0 with glacial acetic acid) and methanol (30:70). Detection was carried out at 254 nm using a UV detector with an injection volume of 20 μL and a flow rate of 1.0 mL/min. Force degradation studies included acid, base, oxidation, thermal, and photo-degradation. Results: Under the described conditions, the separation of p-hydroxy benzoic acid, methylparaben, and propylparaben was achieved in less than 12.0 minutes. The concentration ranges for p-hydroxy benzoic acid, methylparaben, and propylparaben were determined to be 1ng - 50 μg/mL, 100ng - 50μg/mL, and 100ng -12μ g/mL, respectively. The linearity, accuracy, and precision of the method were within acceptable ranges. Discussion: Maximum degradation of methylparaben was observed under base and neutral conditions in the first sample and under base and thermal conditions in the second sample. Similarly, maximum degradation of propylparaben was observed under base conditions in the first sample and under neutral and thermal conditions in the second sample. P-hydroxy benzoic acid degradation was observed under all conditions, with the highest degradation occurring in 0.1 N NaOH and 0.1 N HCl at 60°C. Conclusion: The developed method proved to be effective for the determination of methyl and propylparaben, along with their degradation product p-hydroxy benzoic acid, in pharmaceutical formulations. The results of the force degradation study provided valuable insights into the stability of parabens under various conditions, highlighting the importance of monitoring and controlling their degradation in pharmaceutical products.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.2174/0115734129312130240812070549
Arzoo Pannu, Ramesh K. Goyal
Background: S. barbata D. Don, a perennial herb from the Lamiaceae family, is renowned for its medicinal properties, with scutellarin and scutellarein being key bioactive constituents. Aim: In this study, we present the development and validation of a High-Performance Thin- Layer Chromatography (HPTLC) method for the simultaneous quantitative and qualitative analysis of scutellarin and scutellarein in the hydroethanol extract of S. barbata D. Don. Methods: The chromatographic conditions were optimized using different solvent systems, and validation was performed as per ICH guidelines. Results: The mobile phase comprising Ethyl acetate: methanol: formic acid: water (20: 2.7: 0.5: 2) and scanning wavelength set at 254 nm was optimized for study, resulting in distinct and well-separated spots for scutellarin and scutellarein with Rf values of 0.31 and 0.96, respectively. The method was rigorously validated to ensure reliability and reproducibility. Calibration curves exhibited excellent linearity for both scutellarin (r² > 0.98) and scutellarein (r² > 0.99) over a concentration range of 10-30 μg/ml. The developed method underwent thorough validation following ICH guidelines. Validation parameters included accuracy, limit of quantification, limit of detection, linearity, precision, and recovery. The determined concentration of scutellarin and scutellarein in the hydroethanolic extract of S. barbata D. Don was found to be 27.00 μg/mg and 20.16 μg/mg of extract, respectively. Conclusion: This proposed method demonstrates its utility for both qualitative and quantitative analyses of scutellarin and scutellarein in the hydroethanolic extract of S. barbata D. Don, offering a reliable and validated approach for quality control and standardization in the herbal product industry.
背景：S. barbata D. Don 是一种唇形科多年生草本植物，以其药用特性而闻名，其中黄芩苷和黄芩萃取物是其主要的生物活性成分。目的：本研究开发并验证了一种高效薄层色谱（HPTLC）方法，用于同时定量和定性分析豨莶草水乙醇提取物中的黄芩苷和黄芩萃取物。方法：使用不同的溶剂系统优化色谱条件，并根据 ICH 指南进行验证。结果：经优化的流动相为乙酸乙酯：甲醇：甲酸：水（20：2.7：0.5：2），扫描波长为 254 nm，结果表明黄芩苷和黄芩萃取物的色谱图清晰、分离度高，Rf 值分别为 0.31 和 0.96。该方法经过了严格的验证，以确保其可靠性和重现性。在10-30 μg/ml的浓度范围内，黄芩苷和黄芩素的线性关系良好（r² > 0.98）。所开发的方法按照 ICH 指南进行了全面的验证。验证参数包括准确度、定量限、检测限、线性、精密度和回收率。结果表明，在 S. barbata D. Don 的水乙醇提取物中，黄芩苷和黄芩萃取物的测定浓度分别为 27.00 μg/mg 和 20.16 μg/mg。结论所提出的方法证明了它在定性和定量分析巴豆水乙醇提取物中的黄芩苷和黄芩萃取物方面的实用性，为草药产品行业的质量控制和标准化提供了一种可靠、有效的方法。
{"title":"Development and Validation of a High-Performance Thin-Layer Chromatography Method for Simultaneous Qualitative and Quantitative Analysis of Scutellarin and Scutellarein in S. barbata D. Don","authors":"Arzoo Pannu, Ramesh K. Goyal","doi":"10.2174/0115734129312130240812070549","DOIUrl":"https://doi.org/10.2174/0115734129312130240812070549","url":null,"abstract":"Background: S. barbata D. Don, a perennial herb from the Lamiaceae family, is renowned for its medicinal properties, with scutellarin and scutellarein being key bioactive constituents. Aim: In this study, we present the development and validation of a High-Performance Thin- Layer Chromatography (HPTLC) method for the simultaneous quantitative and qualitative analysis of scutellarin and scutellarein in the hydroethanol extract of S. barbata D. Don. Methods: The chromatographic conditions were optimized using different solvent systems, and validation was performed as per ICH guidelines. Results: The mobile phase comprising Ethyl acetate: methanol: formic acid: water (20: 2.7: 0.5: 2) and scanning wavelength set at 254 nm was optimized for study, resulting in distinct and well-separated spots for scutellarin and scutellarein with Rf values of 0.31 and 0.96, respectively. The method was rigorously validated to ensure reliability and reproducibility. Calibration curves exhibited excellent linearity for both scutellarin (r² > 0.98) and scutellarein (r² > 0.99) over a concentration range of 10-30 μg/ml. The developed method underwent thorough validation following ICH guidelines. Validation parameters included accuracy, limit of quantification, limit of detection, linearity, precision, and recovery. The determined concentration of scutellarin and scutellarein in the hydroethanolic extract of S. barbata D. Don was found to be 27.00 μg/mg and 20.16 μg/mg of extract, respectively. Conclusion: This proposed method demonstrates its utility for both qualitative and quantitative analyses of scutellarin and scutellarein in the hydroethanolic extract of S. barbata D. Don, offering a reliable and validated approach for quality control and standardization in the herbal product industry.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"26 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.2174/0115734129323940240809053530
Breno de Almeida Bertassoni, Eduardo Costa Pinto, Magali Silva de Amorim, Marcela Cristina de de Moraes
: Remdesivir (RDV) is a nucleoside analogue prodrug that acts as a viral RNA polymerase inhibitor, triggering chain termination following its incorporation. Approved for the treatment of COVID-19 in 2020, RDV is administered intravenously. This article presents the main physicochemical characteristics of the compound and outlines the most relevant pharmacokinetic and pharmacodynamic aspects. The main analytical methods described in the literature for the detection and quantification of RDV in biological matrices, raw materials, and formulations are presented herein, as well as those for the analysis of degradation products and synthesis impurities. Discussion includes the advantages and disadvantages of these methods, alongside their limits of detection and quantification. Chromatographic methods using a C18 stationary phase, gradient elution with a mobile phase containing up to 100% acetonitrile, and mass spectrometry detection with electron spray ionization in positive mode represent the main choice for RDV determination in biological matrices. While for raw material and formulation analysis, detection is conducted mainly by employing UV in the 237–254 nm range. Impurity detection primarily utilizes C18 columns, isocratic elution with a mobile phase containing up to 70% acetonitrile, and UV detection (237–247 nm). The literature reports fifteen impurities, requiring further RDV stability studies for identifying and quantifying impurities, as well as the development of chiral methods and pharmacopeia standardization.
{"title":"Remdesivir: A Review on Analytical Methods for Drug Substances, Pharmaceutical Formulations, and Biological Matrices","authors":"Breno de Almeida Bertassoni, Eduardo Costa Pinto, Magali Silva de Amorim, Marcela Cristina de de Moraes","doi":"10.2174/0115734129323940240809053530","DOIUrl":"https://doi.org/10.2174/0115734129323940240809053530","url":null,"abstract":": Remdesivir (RDV) is a nucleoside analogue prodrug that acts as a viral RNA polymerase inhibitor, triggering chain termination following its incorporation. Approved for the treatment of COVID-19 in 2020, RDV is administered intravenously. This article presents the main physicochemical characteristics of the compound and outlines the most relevant pharmacokinetic and pharmacodynamic aspects. The main analytical methods described in the literature for the detection and quantification of RDV in biological matrices, raw materials, and formulations are presented herein, as well as those for the analysis of degradation products and synthesis impurities. Discussion includes the advantages and disadvantages of these methods, alongside their limits of detection and quantification. Chromatographic methods using a C18 stationary phase, gradient elution with a mobile phase containing up to 100% acetonitrile, and mass spectrometry detection with electron spray ionization in positive mode represent the main choice for RDV determination in biological matrices. While for raw material and formulation analysis, detection is conducted mainly by employing UV in the 237–254 nm range. Impurity detection primarily utilizes C18 columns, isocratic elution with a mobile phase containing up to 70% acetonitrile, and UV detection (237–247 nm). The literature reports fifteen impurities, requiring further RDV stability studies for identifying and quantifying impurities, as well as the development of chiral methods and pharmacopeia standardization.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"32 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：