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An Overview of Analytical Methods for the Identification and Quantification of Baclofen 巴氯芬的鉴定和定量分析方法综述
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-05-02 DOI: 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 centralskeletal 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 commonlyused 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, capillaryelectrophoresis, 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. Therewere 73 articles reviewed, of which 26 used HPLC for baclofen quantification; the least used was nearinfrared spectroscopy and potentiometry, both with one article identified.This review has shed light on a wide variety of analytical methods that can be used toquantify and identify baclofen. The knowledge provided by the use of these analytical methods makesthis document an important tool for developing pharmaceutical formulations containing baclofen.
巴氯芬是一种强效解痉药,具有镇痛和中枢骨骼肌松弛作用。它是GABA-B类似物,广泛用于治疗痉挛。由于其治疗重要性,制药工业和研究中使用了各种分析技术来测定、鉴定和表征散装材料、生物流体和药物形式中的巴氯芬。本综述旨在收集有关已报道的分析技术的信息,这些技术通常用于鉴定和量化药物形式和生物样品中的巴氯芬。作者使用这些描述符探索了各种经过认证的科学期刊:高效液相色谱、液相色谱-串联质谱、毛细管电泳、差示扫描量热法、傅立叶变换红外光谱、紫外可见光谱、近红外光谱、核磁共振、电位测定法,以及X射线衍射。通过审查中评估的所有方法对药物进行量化是可能的。综述了73篇文章,其中26篇采用高效液相色谱法对巴氯芬进行定量;使用最少的是近红外光谱法和电位法,这两种方法都鉴定了一篇文章。这篇综述揭示了可用于量化和鉴定巴氯芬的各种分析方法。使用这些分析方法所提供的知识使该文件成为开发含有巴氯芬的药物制剂的重要工具。
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引用次数: 0
Experimental and Theoretical Study of Biosurfactants Functionalized Gold Nanoparticles for Mixture Detection and Chiral Recognition of Tryptophan by UV-Vis Spectroscopy 生物表面活性剂功能化金纳米颗粒混合检测及色氨酸手性识别的实验与理论研究
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-04-27 DOI: 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 beenlong 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 electronmicroscope 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 wasstudied 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 notonly 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 wellas the chiral recognition of Trp enantiomers. DFT calculations proved that the interactions of D-Trpwith biosurfactants were the strongest, which contributes to the promotion of aggregation.
色氨酸是一种必需氨基酸,在生物过程中起着重要作用。色氨酸的检测对其生物学和化学研究具有重要意义。此外,色氨酸是一种手性化合物;由于其在生物过程中的重要性,研究人员长期致力于对三聚体的手性识别和感知。采用胆酸钠和脱氧胆酸钠两种生物表面活性剂制备了功能化金纳米粒子(AuNPs),并用透射电镜和电位计对其进行了表征。分析了不同浓度色氨酸、酪氨酸、苯丙氨酸、d -色氨酸和l -色氨酸的功能化金纳米粒子溶液的紫外可见光谱。然后,进一步研究了生物表面活性剂的识别机理,并利用密度泛函理论(DFT)研究了生物表面活性剂的促进机理。色氨酸能诱导未修饰的AuNPs在2h内聚集,而苯丙氨酸和酪氨酸则不能。添加生物表面活性剂促进了聚合过程,并且发现D-色氨酸而不是LTrp对聚合起作用。因此,不仅色氨酸、苯丙氨酸和酪氨酸之间存在相互作用差异,而且色氨酸对映体之间也存在相互作用差异。紫外可见光谱可用于混合物中色氨酸的直接检测以及色氨酸对映体的手性识别。DFT计算证明,d - trp与生物表面活性剂的相互作用最强,这有助于促进聚集。
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引用次数: 0
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 磷酸西他列汀和达格列嗪丙二醇固定剂量复方双层片同时定量分析反相高效液相色谱法的建立与验证
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-04-17 DOI: 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 phosphatemonohydrate-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 methodvalidation. RP-HPLC analysis was conducted using an ultraviolent absorption spectrophotometer anda Zorbax C18 column (4.6 x 150 mm, 5 µm). The flow rate and injection volume were set to 1.5 mLmin-1 and 20 µL, respectively. The wavelength was set at 205 nm.The retention times of sitagliptin phosphate monohydrate and dapagliflozin propanediolmonohydrate were 2.28 mins and 10.65 mins, respectively. The relative standard deviations of thesystem suitability for validation of simultaneous quantitative analysis were 0.03% for sitagliptin phosphate monohydrate and dapagliflozin propanediol monohydrate. The chromatogram confirmed thatthere was no peak interference between the two main components and between the main componentand the excipients. In addition, It revealed a favorable linearity with correlation coefficients of 0.9999in the concentration range of 20–120% compared to the standard solution.The developed simultaneous quantitative analysis shortened the analysis time and highefficiency 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 behelpful in developing an analytical method by referring to the simultaneous quantitative analysismethod 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。
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引用次数: 0
Survey on Multi-omics, and Multi-omics Data Analysis, Integration and Application 多组学研究综述及多组学数据分析、集成与应用
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-04-06 DOI: 10.2174/1573412919666230406100948
Multi-omics approaches have developed as a profitable technique for plant systems, apopular 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 ofvariability 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 popularpublications developing new approaches. Omics reveal interesting tools to produce behavioraland interactions data in microbial communities, and integrating omics details into microbial riskassessment 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 appropriatefor treatment optimization, molecular testing and disease prognosis, and to achieve mechanisticunderstandings of diseases. New effective solutions for multi-omics data analysis together withwell-designed components are recommended for many trials. The goal of this mini-review articleis to introduce multi-omics technologies considering different multi-omics analyses.
多组学方法已经发展成为一种有益的植物系统技术,在医学和生物科学中流行的方法,强调了概述新的综合技术和功能以促进生物系统多尺度描述的必要性。通过不同的组学层来理解一个生物系统,揭示了可变性的补充来源,并可能推断出导致确定过程的病例序列。在PubMed检索论文及综述,检索关键词为:多组学、数据分析、组学、数据分析、数据集成、深度学习多组学、多组学集成。2010年以后发表的文章被优先考虑。作者主要关注开发新方法的流行出版物。组学揭示了在微生物群落中产生行为和相互作用数据的有趣工具,并且将组学细节整合到微生物风险评估中将对食品安全以及相关的腐败控制程序产生影响。组学数据集在分子水平上全面表征生物病例,在维度和复杂性上都在不断增加。多组学数据分析适用于治疗优化、分子检测和疾病预后,实现对疾病的机制认识。多组学数据分析的新有效解决方案以及精心设计的组件被推荐用于许多试验。这篇小型综述文章的目的是介绍多组学技术考虑不同的多组学分析。
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引用次数: 0
Validation of the T–47D Cell Culture Bioassay for the Potency Assessment of Botulinum Neurotoxin Type A T-47D细胞培养法测定A型肉毒杆菌神经毒素效价的验证
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-20 DOI: 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.
肉毒杆菌神经毒素(bont)是已知的最有效的毒素之一,也用于治疗和美容应用。研究人员开发并验证了另一种体外细胞培养生物测定方法,该方法基于暴露于BoNTA后T - 47D乳腺癌细胞诱导凋亡。T-47D细胞(ATCC HTB−133)以3 × 105 cells mL−1的密度接种,BoNTA剂量为3 ~ 81 U mL−1进行生物测定。用10µL Alamar Blue®评价反应。在570和600 nm处测定吸光度。结果与体内LD50小鼠生物测定结果比较,估计效价的平均差异为1.08% (p < 0.05)。此外,通过尺寸排除法和反相液相色谱法对生物制药进行分析,发现与细胞培养生物测定相关的值分别高1.15%和低0.85%。结论是,经过验证的T - 47D细胞培养试验代表了在3rs背景下建立一种替代效价评估方法的进步。此外,色谱方法与生物测定相结合的使用有助于评估BoNTA生物制药配方的质量属性。
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引用次数: 0
Stability Study and Simultaneous determination of Norepinephrine, Moxifloxacin, and Piperacillin + Tazobactam Mixtures applied in Intensive Care Medicine 重症医学中去甲肾上腺素、莫西沙星、哌拉西林+他唑巴坦合剂的稳定性研究及同时测定
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-15 DOI: 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
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引用次数: 0
Investigation of the Pharmacokinetic Properties and Theoretical Chemical Activities of 7,8-Dihydroxyflavone and 4'-Dimethylamino-7,8-Dihydroxyflavone 7,8-二羟基黄酮和4'-二甲氨基-7,8-二羟基黄酮的药代动力学性质及理论化学活性研究
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-13 DOI: 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.
黄酮类化合物作为次生代谢产物天然存在于植物中。在本研究中,目的是测定和比较7,8-二羟基黄酮(7,8-DHF)和4’-二甲基氨基-7,8-二羟基黄酮的理论和体内化学活性,4’-DMA-7,8-DHF是酪氨酸受体激酶B(TrkB)受体激动剂黄酮分子,据报道具有强大的神经保护作用。BDNF被认为是通过其受体TrkB对抗神经系统疾病的有效治疗剂。然而,BDNF的药代动力学特性较差,不能穿过血脑屏障。研究表明,7,8-DHF和4'-DMA-7,8-DHF可以结合并激活TrkB受体,并通过血脑屏障。人们认为,4’’-DMA-7,8-DHF可能比7,8-DHF更有效,因为在较低浓度下具有较强的TrkB活性并支持神经发生。然而,目前还没有对此进行详细的研究。理论化学分析采用了这种方法。在体内研究中,6个月大的Wistar大鼠分为两组(n=8)。7,8-DHF和4’-DMA-7,8-DHF(5mg/kg)腹膜内(ip)给药。然后,通过颈动脉导管插入术收集血浆样本,并通过微透析技术同时收集清醒大鼠的脑样本12小时。分析血液和脑样品中7,8-DHF和4'-DMA-7,8-DHF的水平,并测定其药代动力学。黄酮类化合物作为次生代谢产物天然存在于植物中。在本研究中,目的是测定和比较7,8-DHF和4’-DMA-7,8-DHF,酪氨酸受体激酶B(TrkB)受体激动剂类黄酮分子的理论和体内化学活性,这些分子具有强大的神经保护作用。理论计算表明,7,8-DHF比4'-DMA-7,8-DHF更稳定。体内药代动力学结果显示,7,8-DHF的最大浓度约为48 ng/mL,而4'-DMA-7,8-DHF仅为8 ng/mL。我们的结果表明,4'-DMA-7,8-DHF比7,8-DHF.更不稳定,更容易与TrkB结合。另一方面,体内药代动力学结果表明,当以治疗浓度全身应用时,7,8-DHF比4'-DMA-7,8-DHF更稳定。理论计算表明,7,8-DHF比4'-DMA-7,8-DHF更稳定。体内药代动力学结果表明,7,8-DHF的最大浓度约为48ng/mL,而4'-DMA-7,8-DHF.的最大浓度仅为8ng/mL。7.8-DHF似乎更适合药理学应用。
{"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}
引用次数: 0
The Metabolism of Portulacatone B from Portulaca oleracea L. in rats by UHPLC-ESI-Q-TOF/MS UHPLC-ESI-Q-TOF/MS研究马齿苋酮B在大鼠体内的代谢
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-06 DOI: 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
目的:研究马齿苋科生物碱马齿苋酮B在大鼠体内的主要代谢产物和代谢途径。研究表明,马齿苋酮B具有良好的抗炎和抗胆碱酯酶活性,这一点有待进一步研究。Portulacatone B通过大鼠的尾静脉给药,在10分钟和30分钟时收集眼眶血,并在24小时内收集尿液和粪便。采用超高效液相色谱-电喷雾-四极杆飞行时间质谱联用技术(UHPLC-ESI-Q-TOF/MS)研究了马齿苋酮B在大鼠体内的主要代谢产物和代谢途径,从马齿苋中分离得到的生物碱。对马齿苋酮B的代谢产物和代谢途径的研究结果表明,经大鼠尾静脉给药后,在血浆样品中发现3种代谢产物,在尿液样品中发现2种代谢产物和在粪便样品中发现1种代谢产物。主要代谢途径是氧化、水解、甲基化、葡萄糖醛酸化和磺化。Portulacatone B通过大鼠的尾静脉给药,收集10分钟和30分钟的眼眶血以及24小时内的尿液和粪便。采用超高效液相色谱-电喷雾-四极杆飞行时间质谱联用技术(UHPLC-ESI-Q-TOF/MS)对大鼠体内代谢产物和代谢途径进行了研究,在大鼠血浆、尿液和粪便样品中发现6种代谢产物,代谢途径包括氧化、水解、甲基化、葡萄糖醛酸化和磺化过程。对马齿苋酮B的代谢产物和代谢途径的研究结果表明,通过大鼠尾静脉给药后,在血浆样品中发现3种代谢产物;尿液样品中的2种代谢产物和粪便样品中的一种代谢产物。主要的代谢途径是氧化、水解、甲基化、葡萄糖醛酸化和磺化
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引用次数: 0
A REVIEW: DRUG EXCIPIENT IINCOMPATIBLITY BY FTIR SPECTROSCOPY 红外光谱法研究药物赋形剂不配伍
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-28 DOI: 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.
对于各种配方的开发,有必要检查药物赋形剂的不相容性。药物与辅料是否配伍。因为药物-赋形剂相互作用研究提供了药物的稳定性数据和药物的保质期。傅里叶变换红外光谱是评价药物赋形剂不配伍性研究的最佳方法。FTIR光谱理论是基于这样一种观点,即分子有吸收特定光频率的倾向,这些光频率对分子的相应结构是独特的。能量取决于原子质量、相关的振动耦合和分子表面的几何形状。例如,分子可能能够吸收入射光中的能量,这将导致它旋转得更快或振动得更大声。本文讨论了具有不同赋形剂的各种药物的清单。本文以近10 ~ 12年的傅立叶变换红外光谱研究成果为基础,重点介绍了药物与多种辅料相互作用的实例,并对红外光谱的原理、工作和应用进行了讨论。
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引用次数: 0
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 超高效液相色谱-质谱联用法研究紫荆根乙醇提取物中丹参苷在大鼠体内的药动学及组织分布
IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-23 DOI: 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
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引用次数: 0
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Current Pharmaceutical Analysis
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