Pub Date : 2023-05-02DOI: 10.2174/1573412919666230502124837
João Augusto Oshiro-Junior, Milena Nogueira da Silva, João Victor Belo da Silva, Naara Felipe da Fonsêca, Ana Claudia Dantas Medeiros
Baclofen is a potent antispasmodic agent, acting as an analgesic and central skeletal muscle relaxant. It is a GABA-B analog, and is widely used for the treatment of spasticity. Due to its therapeutic importance, various analytical techniques are used in the pharmaceutical industry and research to determine, identify, and characterize baclofen in bulk material, biological fluids, and pharmaceutical forms. This review aimed to collect information on reported analytical techniques commonly used to identify and quantify baclofen in pharmaceutical forms and biological samples. The authors explored various authenticated scientific journals using these descriptors: highperformance liquid chromatography, liquid chromatography-tandem mass spectrometry, capillary electrophoresis, differential scanning calorimetry, Fourier transform infrared spectroscopy, ultravioletvisible spectroscopy, near-infrared spectroscopy, nuclear magnetic resonance, potentiometry, and Xray diffraction. Quantification of the drug by all the methods evaluated in the review was possible. There were 73 articles reviewed, of which 26 used HPLC for baclofen quantification; the least used was near infrared spectroscopy and potentiometry, both with one article identified. This review has shed light on a wide variety of analytical methods that can be used to quantify and identify baclofen. The knowledge provided by the use of these analytical methods makes this document an important tool for developing pharmaceutical formulations containing baclofen.
{"title":"An Overview of Analytical Methods for the Identification and Quantification of Baclofen","authors":"João Augusto Oshiro-Junior, Milena Nogueira da Silva, João Victor Belo da Silva, Naara Felipe da Fonsêca, Ana Claudia Dantas Medeiros","doi":"10.2174/1573412919666230502124837","DOIUrl":"https://doi.org/10.2174/1573412919666230502124837","url":null,"abstract":"\u0000\u0000Baclofen is a potent antispasmodic agent, acting as an analgesic and central\u0000skeletal muscle relaxant. It is a GABA-B analog, and is widely used for the treatment of spasticity.\u0000Due to its therapeutic importance, various analytical techniques are used in the pharmaceutical industry and research to determine, identify, and characterize baclofen in bulk material, biological fluids,\u0000and pharmaceutical forms.\u0000\u0000\u0000\u0000This review aimed to collect information on reported analytical techniques commonly\u0000used to identify and quantify baclofen in pharmaceutical forms and biological samples.\u0000\u0000\u0000\u0000The authors explored various authenticated scientific journals using these descriptors: highperformance liquid chromatography, liquid chromatography-tandem mass spectrometry, capillary\u0000electrophoresis, differential scanning calorimetry, Fourier transform infrared spectroscopy, ultravioletvisible spectroscopy, near-infrared spectroscopy, nuclear magnetic resonance, potentiometry, and Xray diffraction.\u0000\u0000\u0000\u0000Quantification of the drug by all the methods evaluated in the review was possible. There\u0000were 73 articles reviewed, of which 26 used HPLC for baclofen quantification; the least used was near\u0000infrared spectroscopy and potentiometry, both with one article identified.\u0000\u0000\u0000\u0000This review has shed light on a wide variety of analytical methods that can be used to\u0000quantify and identify baclofen. The knowledge provided by the use of these analytical methods makes\u0000this document an important tool for developing pharmaceutical formulations containing baclofen.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45314297","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 : 2023-04-27DOI: 10.2174/1573412919666230427110327
Lu Huang, Xiangzong Wu, Yanxia Li, Yiting Chen, Zhenli Qiu
Tryptophan (Trp) is an essential amino acid and plays important roles in biological processes. The detection of Trp is very important for its biological and chemical study. Moreover, Trp is a chiral compound; due to its importance in biological processes, researchers have been long committed to the chiral recognition and sensing of Trp enantiomers. Two biosurfactants, sodium cholate and sodium deoxycholate, were used for the preparation of functionalized gold nanoparticles (AuNPs) which were characterized by transmission electron microscope and potentiometer. UV-Vis spectra of functionalized gold nanoparticle solutions with different concentrations of Trp, tyrosine, phenylalanine, D-Trp, and L-Trp were analyzed. Then, the discrimination mechanism was further investigated, and the promotion mechanism of biosurfactants was studied by density functional theory (DFT). Trp could induce the aggregation of unmodified AuNPs in 2 h, while phenylalanine and tyrosine could not. Adding biosurfactants promoted the aggregation process, and D- Trp rather than LTrp was found to be responsible for the aggregation. Therefore, there were interaction differences not only between Trp, phenylalanine, and tyrosine but also between Trp enantiomers. UV-vis spectroscopy could be applied for the direct detection of Trp in mixtures as well as the chiral recognition of Trp enantiomers. DFT calculations proved that the interactions of D-Trp with biosurfactants were the strongest, which contributes to the promotion of aggregation.
{"title":"Experimental and Theoretical Study of Biosurfactants Functionalized Gold Nanoparticles for Mixture Detection and Chiral Recognition of Tryptophan by UV-Vis Spectroscopy","authors":"Lu Huang, Xiangzong Wu, Yanxia Li, Yiting Chen, Zhenli Qiu","doi":"10.2174/1573412919666230427110327","DOIUrl":"https://doi.org/10.2174/1573412919666230427110327","url":null,"abstract":"\u0000\u0000Tryptophan (Trp) is an essential amino acid and plays important roles in biological processes. The detection of Trp is very important for its biological and chemical study. Moreover, Trp is a chiral compound; due to its importance in biological processes, researchers have been\u0000long committed to the chiral recognition and sensing of Trp enantiomers.\u0000\u0000\u0000\u0000Two biosurfactants, sodium cholate and sodium deoxycholate, were used for the preparation of functionalized gold nanoparticles (AuNPs) which were characterized by transmission electron\u0000microscope and potentiometer. UV-Vis spectra of functionalized gold nanoparticle solutions with different concentrations of Trp, tyrosine, phenylalanine, D-Trp, and L-Trp were analyzed. Then, the discrimination mechanism was further investigated, and the promotion mechanism of biosurfactants was\u0000studied by density functional theory (DFT).\u0000\u0000\u0000\u0000Trp could induce the aggregation of unmodified AuNPs in 2 h, while phenylalanine and tyrosine could not. Adding biosurfactants promoted the aggregation process, and D- Trp rather than LTrp was found to be responsible for the aggregation. Therefore, there were interaction differences not\u0000only between Trp, phenylalanine, and tyrosine but also between Trp enantiomers.\u0000\u0000\u0000\u0000UV-vis spectroscopy could be applied for the direct detection of Trp in mixtures as well\u0000as the chiral recognition of Trp enantiomers. DFT calculations proved that the interactions of D-Trp\u0000with biosurfactants were the strongest, which contributes to the promotion of aggregation.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47131843","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 : 2023-04-17DOI: 10.2174/1573412919666230417081123
Joo-Eun Kim, So-Jin Kang
Sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixeddose combination (FDC) dual-layered tablet is used for type 2 diabetes treatment. Simultaneous quantitative analysis can shorten the analysis time of sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablets and increase their efficiency. This study aimed to develop the simultaneous quantitative analysis for sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablet, a type 2 diabetes treatment. Simultaneous quantitative analysis using the rapid and selective reversed-phase highperformance liquid chromatography (RP-HPLC) method was developed and validated using method validation. RP-HPLC analysis was conducted using an ultraviolent absorption spectrophotometer and a Zorbax C18 column (4.6 x 150 mm, 5 µm). The flow rate and injection volume were set to 1.5 mL min-1 and 20 µL, respectively. The wavelength was set at 205 nm. The retention times of sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate were 2.28 mins and 10.65 mins, respectively. The relative standard deviations of the system suitability for validation of simultaneous quantitative analysis were 0.03% for sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate. The chromatogram confirmed that there was no peak interference between the two main components and between the main component and the excipients. In addition, It revealed a favorable linearity with correlation coefficients of 0.9999 in the concentration range of 20–120% compared to the standard solution. The developed simultaneous quantitative analysis shortened the analysis time and high efficiency of the sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC bilayer tablet. The validity of the analytical method was verified through accuracy and precision, detection and quantitation limits, and solution stability tests. In addition, it was thought that it would be helpful in developing an analytical method by referring to the simultaneous quantitative analysis method for developing other FDC dual-layered tablets.
磷酸西他列汀一水合物达格列嗪丙二醇水合物固定酶组合(FDC)双层片用于治疗2型糖尿病。同时定量分析可以缩短磷酸西格列汀一水合物达格列嗪丙二醇一水合物FDC双层片的分析时间,提高其效率。本研究旨在对治疗2型糖尿病的西他列汀磷酸一水合物达格列嗪丙二醇一水合物FDC双层片进行同时定量分析。采用快速选择性反相高效液相色谱(RP-HPLC)方法进行了同时定量分析,并通过方法验证进行了验证。使用超强力吸收分光光度计和Zorbax C18柱(4.6 x 150 mm,5µm)进行RP-HPLC分析。流速和注射体积分别设定为1.5 mLmin-1和20µL。波长设定为205nm。西他列汀磷酸酯一水合物和达格列嗪丙二醇一水合物的保留时间分别为2.28分钟和10.65分钟。同时定量分析验证系统适用性的相对标准偏差为磷酸西格列汀一水合物和达格列嗪丙二醇一水合物0.03%。色谱图证实两种主要成分之间以及主要成分与赋形剂之间没有峰干扰。此外,与标准溶液相比,在20–120%的浓度范围内,其线性良好,相关系数为0.9999。所开发的同时定量分析缩短了西他列汀磷酸酯一水合物达格列嗪丙二醇一水合物FDC双层片的分析时间和高效性。通过准确度和精密度、检测和定量限以及溶液稳定性测试验证了分析方法的有效性。此外,还认为参照其他FDC双层片的同时定量分析方法开发分析方法是有益的。
{"title":"The development and validation of simultaneous quantitative analysis reversed-phase high-performance liquid chromatography for sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate fixed-dose combination dual-layered tablet","authors":"Joo-Eun Kim, So-Jin Kang","doi":"10.2174/1573412919666230417081123","DOIUrl":"https://doi.org/10.2174/1573412919666230417081123","url":null,"abstract":"\u0000\u0000Sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixeddose combination (FDC) dual-layered tablet is used for type 2 diabetes treatment. Simultaneous quantitative analysis can shorten the analysis time of sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablets and increase their efficiency.\u0000\u0000\u0000\u0000This study aimed to develop the simultaneous quantitative analysis for sitagliptin phosphate\u0000monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablet, a type 2 diabetes treatment.\u0000\u0000\u0000\u0000Simultaneous quantitative analysis using the rapid and selective reversed-phase highperformance liquid chromatography (RP-HPLC) method was developed and validated using method\u0000validation. RP-HPLC analysis was conducted using an ultraviolent absorption spectrophotometer and\u0000a Zorbax C18 column (4.6 x 150 mm, 5 µm). The flow rate and injection volume were set to 1.5 mL\u0000min-1 and 20 µL, respectively. The wavelength was set at 205 nm.\u0000\u0000\u0000\u0000The retention times of sitagliptin phosphate monohydrate and dapagliflozin propanediol\u0000monohydrate were 2.28 mins and 10.65 mins, respectively. The relative standard deviations of the\u0000system suitability for validation of simultaneous quantitative analysis were 0.03% for sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate. The chromatogram confirmed that\u0000there was no peak interference between the two main components and between the main component\u0000and the excipients. In addition, It revealed a favorable linearity with correlation coefficients of 0.9999\u0000in the concentration range of 20–120% compared to the standard solution.\u0000\u0000\u0000\u0000The developed simultaneous quantitative analysis shortened the analysis time and high\u0000efficiency of the sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC bilayer tablet. The validity of the analytical method was verified through accuracy and precision, detection and quantitation limits, and solution stability tests. In addition, it was thought that it would be\u0000helpful in developing an analytical method by referring to the simultaneous quantitative analysis\u0000method for developing other FDC dual-layered tablets.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43203505","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 : 2023-04-06DOI: 10.2174/1573412919666230406100948
Multi-omics approaches have developed as a profitable technique for plant systems, a popular method in medical and biological sciences underlining the necessity to outline new integrative technology and functions to facilitate the multi-scale depiction of biological systems. Understanding a biological system through various omics layers reveals supplementary sources of variability and probably inferring the sequence of cases leading to a definitive process. Manuscripts and reviews were searched on PubMed with the keywords of multi-omics, data analysis, omics, data analysis, data integration, deep learning multi-omics, and multi-omics integration. Articles that were published after 2010 were prioritized. The authors focused mainly on popular publications developing new approaches. Omics reveal interesting tools to produce behavioral and interactions data in microbial communities, and integrating omics details into microbial risk assessment will have an impact on food safety, and also on relevant spoilage control procedures. Omics datasets, comprehensively characterizing biological cases at a molecular level, are continually increasing in both dimensionality and complexity. Multi-omics data analysis is appropriate for treatment optimization, molecular testing and disease prognosis, and to achieve mechanistic understandings of diseases. New effective solutions for multi-omics data analysis together with well-designed components are recommended for many trials. The goal of this mini-review article is to introduce multi-omics technologies considering different multi-omics analyses.
{"title":"Survey on Multi-omics, and Multi-omics Data Analysis, Integration and Application","authors":"","doi":"10.2174/1573412919666230406100948","DOIUrl":"https://doi.org/10.2174/1573412919666230406100948","url":null,"abstract":"\u0000\u0000Multi-omics approaches have developed as a profitable technique for plant systems, a\u0000popular method in medical and biological sciences underlining the necessity to outline new integrative technology and functions to facilitate the multi-scale depiction of biological systems. Understanding a biological system through various omics layers reveals supplementary sources of\u0000variability and probably inferring the sequence of cases leading to a definitive process. Manuscripts and reviews were searched on PubMed with the keywords of multi-omics, data analysis,\u0000omics, data analysis, data integration, deep learning multi-omics, and multi-omics integration. Articles that were published after 2010 were prioritized. The authors focused mainly on popular\u0000publications developing new approaches. Omics reveal interesting tools to produce behavioral\u0000and interactions data in microbial communities, and integrating omics details into microbial risk\u0000assessment will have an impact on food safety, and also on relevant spoilage control procedures.\u0000Omics datasets, comprehensively characterizing biological cases at a molecular level, are continually increasing in both dimensionality and complexity. Multi-omics data analysis is appropriate\u0000for treatment optimization, molecular testing and disease prognosis, and to achieve mechanistic\u0000understandings of diseases. New effective solutions for multi-omics data analysis together with\u0000well-designed components are recommended for many trials. The goal of this mini-review article\u0000is to introduce multi-omics technologies considering different multi-omics analyses.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47709311","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 : 2023-03-20DOI: 10.2174/1573412919666230320155755
S. Dalmora, Bruna Xavier, Rafaela Ferreira Perobelli Dumoncel, Clóvis Dervil Appratto Cardoso Jr, F. S. da Silva
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used for therapeutic and aesthetic applications. An alternative in vitro cell culture bioassay based on the induction of apoptosis on T−47D breast cancer cells, after exposure to BoNTA, was developed and validated. The T-47D cells (ATCC HTB−133) were seeded at a density of 3 × 105 cells mL−1, and the bioassay was performed with doses of BoNTA, between 3 and 81 U mL−1. The responses were assessed using 10 µL of Alamar Blue®. The absorbances were read at 570 and 600 nm. The results were compared with those of the in vivo LD50 mouse bioassay, showing a non-significant 1.08% higher, mean difference of the estimated potencies (p>0.05). Besides, the biopharmaceutics is analyzed by the size exclusion and reversed-phase liquid chromatography methods, showing a significant correlation with values 1.15% higher and 0.85% lower, respectively, related to the cell culture bioassay. It is concluded that the validated T−47D cell culture assay represents an advancement toward the establishment of an alternative approach for the potency assessment, in the context of the 3 Rs. Besides, the employment of chromatographic methods in conjunction with the bioassays contributes to assessing the quality attributes of the biopharmaceutical formulations of BoNTA.
{"title":"Validation of the T–47D Cell Culture Bioassay for the Potency Assessment of Botulinum Neurotoxin Type A","authors":"S. Dalmora, Bruna Xavier, Rafaela Ferreira Perobelli Dumoncel, Clóvis Dervil Appratto Cardoso Jr, F. S. da Silva","doi":"10.2174/1573412919666230320155755","DOIUrl":"https://doi.org/10.2174/1573412919666230320155755","url":null,"abstract":"\u0000\u0000Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used for therapeutic and aesthetic applications.\u0000\u0000\u0000\u0000An alternative in vitro cell culture bioassay based on the induction of apoptosis on T−47D breast cancer cells, after exposure to BoNTA, was developed and validated.\u0000\u0000\u0000\u0000The T-47D cells (ATCC HTB−133) were seeded at a density of 3 × 105 cells mL−1, and the bioassay was performed with doses of BoNTA, between 3 and 81 U mL−1. The responses were assessed using 10 µL of Alamar Blue®. The absorbances were read at 570 and 600 nm.\u0000\u0000\u0000\u0000The results were compared with those of the in vivo LD50 mouse bioassay, showing a non-significant 1.08% higher, mean difference of the estimated potencies (p>0.05). Besides, the biopharmaceutics is analyzed by the size exclusion and reversed-phase liquid chromatography methods, showing a significant correlation with values 1.15% higher and 0.85% lower, respectively, related to the cell culture bioassay.\u0000\u0000\u0000\u0000It is concluded that the validated T−47D cell culture assay represents an advancement toward the establishment of an alternative approach for the potency assessment, in the context of the 3 Rs. Besides, the employment of chromatographic methods in conjunction with the bioassays contributes to assessing the quality attributes of the biopharmaceutical formulations of BoNTA.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47917653","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 : 2023-03-15DOI: 10.2174/1573412919666230315151351
J. Schmidt, M. Steppe
In intensive care units intravenous medicine may be used in simultaneous infusion in the same intravenous site. Sometimes, the physical compatibility and stability of the combined solutions are unknown. The objective was to develop, optimize and validate a simple, fast and sensitive stability-indicating high-performance liquid chromatography (HPLC) for simultaneous quantification of binary mixtures of norepinephrine, piperacillin + tazobactam, moxifloxacin for intravenous (IV) administration in different diluents and physical compatibility with mannitol. The HPLC method was performed on a C18LUNA (4.6x250 mm 5-Micron) column, using acetonitrile: methanol: phosphate buffer pH 3.0 (20:30:50) as eluent and validated according to ICH guidelines and applied to mixtures of norepinephrine, moxifloxacin, piperacillin, tazobactam and mannitol at 0, 2, 6, 9 and 24 h. The substances and their mixtures were also evaluated by visual inspection and pH over time. The analytical method developed was specific, linear, precise, accurate and robust. No visual changes were observed in the mixtures over time, maintaining the pH values (except for piperacillin + tazobactam which changed 0.5 in 24 h) and losses of less than 10% of content over the 24 h under analyzed conditions. The proposed method is suitable for simultaneous analysis of norepinephrine, moxifloxacin, piperacillin and tazobactam. All tested mixtures were compatible and stable for up to 24 h, which is an important result for increasing patient safety in clinical practice since it has not been reported in the literature yet. The method can be further investigated and used for different concentration and diluent combinations. Conclusion: The proposed method is suitable for simultaneous analysis of norepinephrine, moxifloxacin, piperacillin and tazobactam. All tested mixtures were compatible and stable for up to 24 h, which is an important result for increase patient safety in clinical practice, since it has not been reported in literature yet. The method can be further investigated and used for different concentration and diluents combinations. HPLC
在重症监护病房,静脉药物可以在同一静脉部位同时输注。有时,组合溶液的物理相容性和稳定性是未知的。目的:建立、优化并验证一种简便、快速、灵敏且具有稳定性指示的高效液相色谱法(HPLC),用于同时定量不同稀释度的去甲肾上腺素、哌拉西林+他唑巴坦、莫西沙星静脉注射用二元混合物及其与甘露醇的物理相容性。HPLC法采用C18LUNA (4.6x250 mm 5微米)色谱柱,乙腈:甲醇:磷酸盐缓冲液pH 3.0(20:30:50)为洗脱液,根据ICH指南进行验证,并适用于去甲肾上腺素、莫西沙星、哌拉西林、他唑巴坦和甘露醇的混合物,分别在0、2、6、9和24 h。通过目测和pH随时间的变化对物质及其混合物进行评价。所建立的分析方法具有专属性、线性、精密度、准确度和鲁棒性。随着时间的推移,没有观察到混合物的视觉变化,保持pH值(除了哌拉西林+他唑巴坦在24小时内变化0.5),在分析条件下,24小时内含量损失小于10%。该方法适用于去甲肾上腺素、莫西沙星、哌拉西林和他唑巴坦的同时分析。所有测试的混合物在长达24小时内均具有相容性和稳定性,这是提高临床实践中患者安全性的重要结果,因为尚未有文献报道。该方法可以进一步研究,并用于不同的浓度和稀释剂组合。结论:该方法适用于去甲肾上腺素、莫西沙星、哌拉西林和他唑巴坦的同时分析。所有测试的混合物在长达24小时内都是相容和稳定的,这是在临床实践中提高患者安全性的重要结果,因为尚未有文献报道。该方法可以进一步研究,并用于不同的浓度和稀释剂组合。高效液相色谱法
{"title":"Stability Study and Simultaneous determination of Norepinephrine, Moxifloxacin, and Piperacillin + Tazobactam Mixtures applied in Intensive Care Medicine","authors":"J. Schmidt, M. Steppe","doi":"10.2174/1573412919666230315151351","DOIUrl":"https://doi.org/10.2174/1573412919666230315151351","url":null,"abstract":"\u0000\u0000In intensive care units intravenous medicine may be used in simultaneous infusion in the same intravenous site. Sometimes, the physical compatibility and stability of the combined solutions are unknown.\u0000\u0000\u0000\u0000The objective was to develop, optimize and validate a simple, fast and sensitive stability-indicating high-performance liquid chromatography (HPLC) for simultaneous quantification of binary mixtures of norepinephrine, piperacillin + tazobactam, moxifloxacin for intravenous (IV) administration in different diluents and physical compatibility with mannitol.\u0000\u0000\u0000\u0000The HPLC method was performed on a C18LUNA (4.6x250 mm 5-Micron) column, using acetonitrile: methanol: phosphate buffer pH 3.0 (20:30:50) as eluent and validated according to ICH guidelines and applied to mixtures of norepinephrine, moxifloxacin, piperacillin, tazobactam and mannitol at 0, 2, 6, 9 and 24 h. The substances and their mixtures were also evaluated by visual inspection and pH over time.\u0000\u0000\u0000\u0000The analytical method developed was specific, linear, precise, accurate and robust. No visual changes were observed in the mixtures over time, maintaining the pH values (except for piperacillin + tazobactam which changed 0.5 in 24 h) and losses of less than 10% of content over the 24 h under analyzed conditions.\u0000\u0000\u0000\u0000The proposed method is suitable for simultaneous analysis of norepinephrine, moxifloxacin, piperacillin and tazobactam. All tested mixtures were compatible and stable for up to 24 h, which is an important result for increasing patient safety in clinical practice since it has not been reported in the literature yet. The method can be further investigated and used for different concentration and diluent combinations.\u0000\u0000\u0000\u0000Conclusion: The proposed method is suitable for simultaneous analysis of norepinephrine, moxifloxacin, piperacillin and tazobactam. All tested mixtures were compatible and stable for up to 24 h, which is an important result for increase patient safety in clinical practice, since it has not been reported in literature yet. The method can be further investigated and used for different concentration and diluents combinations.\u0000\u0000\u0000\u0000HPLC\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48854962","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 : 2023-03-13DOI: 10.2174/1573412919666230313143549
O. Korkmaz, M. F. Karakaya, Faik Gokalp, E. Şener
Flavonoids naturally exist in plants as secondary metabolites. In this study, the aim is to determine and compare the theoretical and in vivo chemical activities of 7,8-dihydroxyflavone (7,8-DHF) and 4'dimethylamino-7,8-dihydroxyflavone (4’-DMA-7,8-DHF), tyrosine receptor kinase B (TrkB) receptor agonist flavonoid molecules with reported potent neuroprotective effects. BDNF has been thought to be a potent therapeutic agent against neurological disorders via its receptor TrkB. However, BDNF has poor pharmacokinetic properties and cannot cross the blood-brain barrier. It has been demonstrated that 7,8-DHF and 4''-DMA-7,8-DHF can bind and activate TrkB receptors and pass the blood-brain barrier. It has been thought that 4''-DMA-7,8-DHF may be more potent than 7,8-DHF due to strong TrkB activity and supporting neurogenesis at lower concentrations. However, there is no detailed study on this yet. method was used for the theoretical chemical analysis. For the in vivo studies, 6-month-old Wistar rats were used in two groups (n=8). 7,8-DHF and 4’-DMA-7,8-DHF (5 mg/kg) were administered intraperitoneally (ip) to each group. Then, plasma samples were collected by carotid catheterization, and brain samples by the microdialysis technique were collected simultaneously for 12 h from awake rats. The level of 7,8-DHF and 4’-DMA-7,8-DHF in blood and brain samples were analyzed and their pharmacokinetics were determined. Flavonoids naturally exist in plants as seconder metabolites. In this study, the aim is to determine and compare the theoretical and in vivo chemical activities of 7,8-DHF and 4’-DMA-7,8-DHF, tyrosine receptor kinase B (TrkB) receptor agonist flavonoid molecules with reported potent neuroprotective effects. Theoretical calculations show that 7,8-DHF is slightly more stable than 4’-DMA-7,8-DHF. The in vivo pharmacokinetic results show that the maximum concentration of 7,8-DHF was about 48 ng/mL, whereas it was only 8 ng/mL for 4’-DMA-7,8-DHF. Our results suggest that the 4'-DMA-7,8-DHF is more unstable and is more prone to binding to TrkB than 7,8-DHF. On the other hand, the in vivo pharmacokinetic results show that 7,8-DHF is more stable than 4’-DMA-7,8-DHF when it is applied systemically at therapeutic concentrations. Theoretical calculations show that 7,8-DHF is slightly more stable than 4’-DMA-7,8-DHF. The in vivo pharmacokinetic results show that the maximum concentration of 7,8-DHF was about 48 ng/mL, whereas it was only 8 ng/mL for 4’-DMA-7,8-DHF. 7.8-DHF seems more suitable for pharmacological applications.
{"title":"Investigation of the Pharmacokinetic Properties and Theoretical Chemical Activities of 7,8-Dihydroxyflavone and 4'-Dimethylamino-7,8-Dihydroxyflavone","authors":"O. Korkmaz, M. F. Karakaya, Faik Gokalp, E. Şener","doi":"10.2174/1573412919666230313143549","DOIUrl":"https://doi.org/10.2174/1573412919666230313143549","url":null,"abstract":"\u0000\u0000Flavonoids naturally exist in plants as secondary metabolites. In this study, the aim is to determine and compare the theoretical and in vivo chemical activities of 7,8-dihydroxyflavone (7,8-DHF) and 4'dimethylamino-7,8-dihydroxyflavone (4’-DMA-7,8-DHF), tyrosine receptor kinase B (TrkB) receptor agonist flavonoid molecules with reported potent neuroprotective effects.\u0000\u0000\u0000\u0000BDNF has been thought to be a potent therapeutic agent against neurological disorders via its receptor TrkB. However, BDNF has poor pharmacokinetic properties and cannot cross the blood-brain barrier. It has been demonstrated that 7,8-DHF and 4''-DMA-7,8-DHF can bind and activate TrkB receptors and pass the blood-brain barrier. It has been thought that 4''-DMA-7,8-DHF may be more potent than 7,8-DHF due to strong TrkB activity and supporting neurogenesis at lower concentrations. However, there is no detailed study on this yet.\u0000\u0000\u0000\u0000method was used for the theoretical chemical analysis. For the in vivo studies, 6-month-old Wistar rats were used in two groups (n=8). 7,8-DHF and 4’-DMA-7,8-DHF (5 mg/kg) were administered intraperitoneally (ip) to each group. Then, plasma samples were collected by carotid catheterization, and brain samples by the microdialysis technique were collected simultaneously for 12 h from awake rats. The level of 7,8-DHF and 4’-DMA-7,8-DHF in blood and brain samples were analyzed and their pharmacokinetics were determined.\u0000\u0000\u0000\u0000Flavonoids naturally exist in plants as seconder metabolites. In this study, the aim is to determine and compare the theoretical and in vivo chemical activities of 7,8-DHF and 4’-DMA-7,8-DHF, tyrosine receptor kinase B (TrkB) receptor agonist flavonoid molecules with reported potent neuroprotective effects.\u0000\u0000\u0000\u0000Theoretical calculations show that 7,8-DHF is slightly more stable than 4’-DMA-7,8-DHF. The in vivo pharmacokinetic results show that the maximum concentration of 7,8-DHF was about 48 ng/mL, whereas it was only 8 ng/mL for 4’-DMA-7,8-DHF.\u0000\u0000\u0000\u0000Our results suggest that the 4'-DMA-7,8-DHF is more unstable and is more prone to binding to TrkB than 7,8-DHF. On the other hand, the in vivo pharmacokinetic results show that 7,8-DHF is more stable than 4’-DMA-7,8-DHF when it is applied systemically at therapeutic concentrations.\u0000\u0000\u0000\u0000Theoretical calculations show that 7,8-DHF is slightly more stable than 4’-DMA-7,8-DHF. The in vivo pharmacokinetic results show that the maximum concentration of 7,8-DHF was about 48 ng/mL, whereas it was only 8 ng/mL for 4’-DMA-7,8-DHF.\u0000\u0000\u0000\u00007.8-DHF seems more suitable for pharmacological applications.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47503732","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 : 2023-03-06DOI: 10.2174/1573412919666230306124751
Aijing Leng, Xixiang Ying, Xinyu Cui, Xiujuan Lan
Objective: This study aims to investigate the main metabolites and metabolic pathways of Portulacatone B in rats, which is an alkaloid isolated from Portulaca oleracea L. Portulaca oleracea L. is an edible and medicinal plant belonging to the family of Portulacaceae, with rich pharmacological effects mainly attributed to its active ingredients. Studies have shown that Portulacatone B has excellent anti-inflammatory and anticholinesterase activity, which was further investigated. Portulacatone B was administered through the tail vein of the rat, and the orbital blood at 10 and 30 min and urine and feces within 24 h were collected. The metabolites and metabolic pathways in the rat were researched by ultra-high performance liquid chromatography-electrospray coupled with quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS). This study aims to investigate the main metabolites and metabolic pathways of Portulacatone B in rats, which was an alkaloid isolated from Portulaca oleracea L. The research results of the metabolites and metabolic pathways of Portulacatone B showed that after administration through the tail vein of rats, 3 metabolites were found in the plasma sample, 2 metabolites in the urine sample, and one metabolite in the feces sample. The main metabolic pathways were found to be oxidation, hydrolysis, methylation, glucuronidation, and sulfonation. Portulacatone B was administered through the tail vein of the rat, the orbital blood of 10 and 30 min and urine and feces within 24 h were collected. The metabolites and metabolic pathway in the rat were researched by ultra-high performance liquid chromatography electrospray coupled with quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS). Six metabolites were found in the rat’s plasma, urine, and feces samples, and the metabolic pathways included oxidation, hydrolysis, methylation, glucuronidation, and sulfonation process. The research results of the metabolites and metabolic pathways of Portulacatone B showed that after administration through the tail vein of rats, 3 metabolites were found in the plasma sample; 2 metabolites in the urine sample, and a metabolite in the feces sample. The main metabolic pathways are oxidation, hydrolysis, methylation, glucuronidation, and sulfonation. not
{"title":"The Metabolism of Portulacatone B from Portulaca oleracea L. in rats by UHPLC-ESI-Q-TOF/MS","authors":"Aijing Leng, Xixiang Ying, Xinyu Cui, Xiujuan Lan","doi":"10.2174/1573412919666230306124751","DOIUrl":"https://doi.org/10.2174/1573412919666230306124751","url":null,"abstract":"\u0000\u0000Objective: This study aims to investigate the main metabolites and metabolic pathways of Portulacatone B in rats, which is an alkaloid isolated from Portulaca oleracea L.\u0000\u0000\u0000\u0000Portulaca oleracea L. is an edible and medicinal plant belonging to the family of Portulacaceae, with rich pharmacological effects mainly attributed to its active ingredients. Studies have shown that Portulacatone B has excellent anti-inflammatory and anticholinesterase activity, which was further investigated.\u0000\u0000\u0000\u0000Portulacatone B was administered through the tail vein of the rat, and the orbital blood at 10 and 30 min and urine and feces within 24 h were collected. The metabolites and metabolic pathways in the rat were researched by ultra-high performance liquid chromatography-electrospray coupled with quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS).\u0000\u0000\u0000\u0000This study aims to investigate the main metabolites and metabolic pathways of Portulacatone B in rats, which was an alkaloid isolated from Portulaca oleracea L.\u0000\u0000\u0000\u0000The research results of the metabolites and metabolic pathways of Portulacatone B showed that after administration through the tail vein of rats, 3 metabolites were found in the plasma sample, 2 metabolites in the urine sample, and one metabolite in the feces sample. The main metabolic pathways were found to be oxidation, hydrolysis, methylation, glucuronidation, and sulfonation.\u0000\u0000\u0000\u0000Portulacatone B was administered through the tail vein of the rat, the orbital blood of 10 and 30 min and urine and feces within 24 h were collected. The metabolites and metabolic pathway in the rat were researched by ultra-high performance liquid chromatography electrospray coupled with quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS).\u0000\u0000\u0000\u0000Six metabolites were found in the rat’s plasma, urine, and feces samples, and the metabolic pathways included oxidation, hydrolysis, methylation, glucuronidation, and sulfonation process.\u0000\u0000\u0000\u0000The research results of the metabolites and metabolic pathways of Portulacatone B showed that after administration through the tail vein of rats, 3 metabolites were found in the plasma sample; 2 metabolites in the urine sample, and a metabolite in the feces sample. The main metabolic pathways are oxidation, hydrolysis, methylation, glucuronidation, and sulfonation.\u0000\u0000\u0000\u0000not\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48617871","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 : 2023-02-28DOI: 10.2174/1573412919666230228102158
S. Kumari, Chander Singh, K. Rao, Nikita Yadav, Nidhi Bansal, Yogesh Vashist, Palak Chugh
For the development of various formulations, it is necessary to check out the drug excipient incompatibility. Whether the drug is compatible with the excipient or not. Because the drug excipient interaction study provides stability data of the drug and shelf life of the drug. Fourier transform infrared spectroscopy is the best method to evaluate the drug excipient incompatibility study. The FTIR spectroscopy theory is based on the idea that molecules have a tendency to absorb particular light frequencies that are unique to the corresponding structure of the molecules. The energies depend on the atomic masses, the related vibronic coupling, and the geometry of the molecular surfaces. For instance, the molecule may be able to absorb the energy present in the incident light, which will cause it to rotate more quickly or vibrate more loudly. In this article, a list of various drugs with different excipients was discussed. This review emphasizes on various examples of drug interaction with a number of excipients on the basis of Fourier Transform infrared spectroscopy data which is based on last 10-12 year research paper, and the principle ,working, applications of infrared spectroscopy were also discussed.
{"title":"A REVIEW: DRUG EXCIPIENT IINCOMPATIBLITY BY FTIR SPECTROSCOPY","authors":"S. Kumari, Chander Singh, K. Rao, Nikita Yadav, Nidhi Bansal, Yogesh Vashist, Palak Chugh","doi":"10.2174/1573412919666230228102158","DOIUrl":"https://doi.org/10.2174/1573412919666230228102158","url":null,"abstract":"\u0000\u0000For the development of various formulations, it is necessary to check out the drug excipient incompatibility. Whether the drug is compatible with the excipient or not. Because the drug excipient interaction study provides stability data of the drug and shelf life of the drug. Fourier transform infrared spectroscopy is the best method to evaluate the drug excipient incompatibility study. The FTIR spectroscopy theory is based on the idea that molecules have a tendency to absorb particular light frequencies that are unique to the corresponding structure of the molecules. The energies depend on the atomic masses, the related vibronic coupling, and the geometry of the molecular surfaces. For instance, the molecule may be able to absorb the energy present in the incident light, which will cause it to rotate more quickly or vibrate more loudly. In this article, a list of various drugs with different excipients was discussed. This review emphasizes on various examples of drug interaction with a number of excipients on the basis of Fourier Transform infrared spectroscopy data which is based on last 10-12 year research paper, and the principle ,working, applications of infrared spectroscopy were also discussed.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47401152","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 : 2023-02-23DOI: 10.2174/1573412919666230223140457
Guo Feng, Wenjing Wang, Lai-lai Li, Wei Li, Wen Liu, Zeng-guang Wu, Hongmei Su, G. Zhu, Chenchen Ren, Xueli Song, Ju Zhang, Zhengyan He
Daphnoretin, as a known bicoumarin compound that contained various pharmacological activities, was isolated from Wikstroemia indica C.A. Mey (RWI). The study aims to investigate the pharmacokinetic characteristics of daphnoretin from RWI ethanol extracts in rat plasma and to determine daphnetin in rat plasma and various tissues by a rapid, reliable and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method. The UPLC-MS/MS method was established. Daphnoretin and IS (buspirone) were chromatographed on an agilent Zorbax XDB-C18 column (2.1 mm × 50 mm, 3.5 μm), and Gradient elution of acetonitrile-0.15% formic acid in aqueous solution. Quantification was performed using electrospray ionization in positive ion multiple reaction monitoring mode of the transitions m/z 353.1→179.1 for daphnoretin and m/z 386.3→122.3 for IS. Good linearity between 5–10000 ng/mL for cyperidin in plasma and tissue samples (r ≥ 0.99) was resulted. The accuracies of plasma and tissue homogenates ranged from –3.31% to 9.00%, and the precision was less than 5.78%. After that, the validated method was successfully applied to the pharmacokinetics and tissue distribution study of daphnoretin after oral administration of ethanol extract from the roots of RWI to rats. Daphnoretin was well absorbed in the systemic circulation after oral administration and was widely distributed in tissues, with the highest concentration in lung tissue. This study is beneficial to the development and utilization of RWI and provides a reasonable reference for its clinical administration. none
从紫薇属植物(Wikstroemia indica c.a.mey, RWI)中分离得到了一种具有多种药理活性的双香豆素类化合物。本研究旨在研究瑞香乙醇提取物中瑞香素在大鼠血浆中的药动学特征,并建立快速、可靠、灵敏的超高效液相色谱串联质谱法测定大鼠血浆及各组织中瑞香素的含量。建立了UPLC-MS/MS方法。采用agilent Zorbax XDB-C18色谱柱(2.1 mm × 50 mm, 3.5 μm)对丹参素和丁螺环酮进行层析,乙腈-0.15%甲酸水溶液梯度洗脱。采用电喷雾电离法在正离子多反应监测模式下对m/z 353.1→179.1和m/z 386.3→122.3过渡段进行定量。血浆和组织样品中cyperidin含量在5 ~ 10000 ng/mL之间呈良好的线性关系(r≥0.99)。血浆和组织匀浆的准确度为-3.31% ~ 9.00%,精密度小于5.78%。之后,将验证的方法成功应用于大鼠口服大黄根乙醇提取物后大黄皮苷的药代动力学和组织分布研究。口服给药后,瑞香素在体循环中吸收良好,在组织中分布广泛,以肺组织中浓度最高。本研究有利于RWI的开发利用,为其临床应用提供合理参考
{"title":"Pharmacokinetics and Tissue Distribution Study of Daphnoretin in Ethanol Extract from the Roots of Wikstroemia Indica in Rats by a Validated UPLC-MS/MS Method","authors":"Guo Feng, Wenjing Wang, Lai-lai Li, Wei Li, Wen Liu, Zeng-guang Wu, Hongmei Su, G. Zhu, Chenchen Ren, Xueli Song, Ju Zhang, Zhengyan He","doi":"10.2174/1573412919666230223140457","DOIUrl":"https://doi.org/10.2174/1573412919666230223140457","url":null,"abstract":"\u0000\u0000Daphnoretin, as a known bicoumarin compound that contained various pharmacological activities, was isolated from Wikstroemia indica C.A. Mey (RWI).\u0000\u0000\u0000\u0000The study aims to investigate the pharmacokinetic characteristics of daphnoretin from RWI ethanol extracts in rat plasma and to determine daphnetin in rat plasma and various tissues by a rapid, reliable and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method.\u0000\u0000\u0000\u0000The UPLC-MS/MS method was established. Daphnoretin and IS (buspirone) were chromatographed on an agilent Zorbax XDB-C18 column (2.1 mm × 50 mm, 3.5 μm), and Gradient elution of acetonitrile-0.15% formic acid in aqueous solution.\u0000Quantification was performed using electrospray ionization in positive ion multiple reaction monitoring mode of the transitions m/z 353.1→179.1 for daphnoretin and m/z 386.3→122.3 for IS.\u0000\u0000\u0000\u0000Good linearity between 5–10000 ng/mL for cyperidin in plasma and tissue samples (r ≥ 0.99) was resulted. The accuracies of plasma and tissue homogenates ranged from –3.31% to 9.00%, and the precision was less than 5.78%. After that, the validated method was successfully applied to the pharmacokinetics and tissue distribution study of daphnoretin after oral administration of ethanol extract from the roots of RWI to rats.\u0000\u0000\u0000\u0000Daphnoretin was well absorbed in the systemic circulation after oral administration and was widely distributed in tissues, with the highest concentration in lung tissue. This study is beneficial to the development and utilization of RWI and provides a reasonable reference for its clinical administration.\u0000\u0000\u0000\u0000none\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48726586","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}