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1.
For performance assessment of the lipid-based drug delivery systems (LBDDSs), in vitro lipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilization processes. Much of previous research on in vitro lipolysis has mostly focused on rank-ordering formulations for their predicted performances. In this study, we have incorporated in vitro lipolysis with microsomal stability to quantitatively predict the oral bioavailability of a lipophilic antineoplastic drug bexarotene (BEX) administered in LBDDS. Two types of LBDDS were applied: lipid solution and lipid suspension. The predicted oral bioavailability values of BEX from linking in vitro lipolysis with microsomal stability for lipid solution and lipid suspension were 34.2 ± 1.6% and 36.2 ± 2.6%, respectively, whereas the in vivo oral bioavailability of BEX was tested as 31.5 ± 13.4% and 31.4 ± 5.2%, respectively. The predicted oral bioavailability corresponded well with the oral bioavailability for both formulations, demonstrating that the combination of in vitro lipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivo intestinal lymphatic uptake was also assessed for the formulations and resulted in <1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability.  相似文献   
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Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(±)FT-ICR MS) and portable micro near-infrared spectroscopy (microNIR), coupled to sensory analysis, were used to propose a new analytical methodology to observe the characteristics of Robusta coffees cultivated in agroforestry systems (AFS). Principal component analysis (PCA) chemometric models provided excellent discrimination of the samples analyzed by ESI(±)FT-ICR mass spectra for the ground coffee grains. Analysis of the spectra allowed for identification of the compounds responsible for distinguishing the samples grown with different intercropping AFS species. The microNIR results corroborated the ESI(-)FT-ICR MS data and the sensory analysis, by grouping together coffees grown in AFS intercropped with Gliricidia sepium and Inga edulis. The coupling of these analytical techniques shows promise in coffee quality control, presenting advantages such as collection at point analysis, speed, and analytical reliability.  相似文献   
4.
Detection and quantification of drugs from various biological matrices are of immense importance in forensic toxicological analysis. Despite the various reported methods, development of a new method for the detection and quantification of drugs is still an active area of research. However, every method and biological matrix has its own limitation, which further encourage forensic toxicologists to develop new methods and to explore new matrices for the analysis of drugs. In this study, an electrospray ionization‐liquid chromatograph‐tandem mass spectrometry (ESI‐LC‐MS/MS) method is developed and validated for simultaneous identification and quantification of 24 drugs of forensic relevance in various body fluids, namely, whole blood, plasma and vitreous humour. The newly developed method has been validated for intra‐day and inter‐day accuracy, precision, selectivity and sensitivity. Absolute recovery shows a mean of 84.5, 86.2, and 103% in the vitreous humour, whole blood and plasma respectively, which is suitable for the screening procedure. Further, the absolute matrix effect (AME) shows a mean of 105, 96.5, and 109% in the vitreous humour, whole blood and plasma, respectively. In addition, to examine the practical utility of this method, it has been applied for screening of drugs in post‐mortem samples of the vitreous humour, whole blood and plasma collected at autopsy from ten cadavers. Experimental results show that the newly developed method is well applicable for screening of analytes in all the three matrices. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
5.
LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel 18O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H218O in the presence of the enzyme, generating singly- and doubly-18O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.  相似文献   
6.
Recently, 2-aminothiazoline-4-carboxylic acid (ATCA), a cyanide (CN) metabolite, has been proposed as a stable diagnostic marker of CN poisoning. In this study, liquid chromatography coupled with electrospray ionization – tandem mass spectrometry was used to quantify ATCA concentrations in human postmortem blood samples, and differences in ATCA concentrations according to age and sex were determined. Both age and sex had significant effects on blood ATCA concentrations. Although ATCA concentrations exhibited an inverted U shape with increasing age in men, in women ATCA concentrations plateaued at around 40–59 years of age. There were significant differences between the sexes in ATCA concentrations for the 20–39 and 40–59 year age groups (P < 0.05 and P < 0.01, respectively). Correlations between ATCA concentrations and carboxyhemoglobin (CO-Hb) saturation were also examined in fire victims. ATCA concentrations increased significantly with increasing CO-Hb saturation (r = 0.382, P < 0.01). In addition, ATCA concentrations were also correlated to CN concentrations (r = 0.309, P < 0.05). The results of our study may provide novel information about the contribution of CN poisoning to the cause of death at fire scenes.  相似文献   
7.

Objective

To examine the effectiveness of epidural steroid injection (ESI) and back education with and without physical therapy (PT) in individuals with lumbar spinal stenosis (LSS).

Design

Randomized clinical trial.

Setting

Orthopedic spine clinics.

Participants

A total of 390 individuals were screened with 60 eligible and randomly selected to receive ESI and education with or without PT (N=54).

Interventions

A total of 54 individuals received 1-3 injections and education in a 10-week intervention period, with 31 receiving injections and education only (ESI) and 23 additionally receiving 8-10 sessions of multimodal PT (ESI+PT).

Main Outcome Measures

Disability, pain, quality of life, and global rating of change were collected at 10 weeks, 6 months, and 1 year and analyzed using linear mixed model analysis.

Results

No significant difference was found between ESI and ESI+PT in the Oswestry Disability Index at any time point, although the sample had significant improvements at 10 weeks (P<.001; 95% confidence interval [CI], ?18.01 to ?5.51) and 1 year (P=.01; 95% CI, ?14.57 to ?2.03) above minimal clinically important difference. Significant differences in the RAND 36-Item Short Form Health Survey 1.0 were found for ESI+PT at 10 weeks with higher emotional role function (P=.03; 95% CI, ?49.05 to ?8.01), emotional well-being (P=.02; 95% CI, ?19.52 to -2.99), and general health perception (P=.05; 95% CI, ?17.20 to ?.78).

Conclusions

Epidural steroid injection plus PT was not superior to ESI alone for reducing disability in individuals with LSS. Significant benefit was found for the addition of PT related to quality of life factors of emotional function, emotional well-being, and perception of general health.  相似文献   
8.
介绍ESI数据库及其指标体系的特点,分析ESI数据库的应用情况,对科学研究评价工具的功能设计思路进行思考,提出设立权重平衡学科差异、建立人名机构规范档、提高可检索性及可视化程度等建议。  相似文献   
9.
运用h指数、ESI高被引论文、ESI热点论文等文献计量学指标分析Web of ScienceTM上2007-2016年间中国疾病预防控制中心及省级疾病预防控制中心的论文,对比中国疾病预防控制中心、5个SCI论文量最多的省级疾病预防控制中心的学术影响力,提出发挥中国疾病预防控制中心的学术带头作用、各省级疾病预防控制中心在各自研究领域继续发挥所长等建议。  相似文献   
10.
ESI数据库为数据来源,采集金砖四国2004-01-01至2014-06-30发表的论文数据,采用科研论文相对产出、相对引文影响指标分析金砖四国科研论文的产出规模及其影响;并采用学科专业化指标和标准引文影响指标,构建“学科专业化-标准引文影响”二维分析框架,分析金砖四国科研产出在全球的相对位置。研究结果表明,金砖四国科研论文绝对产出较多;金砖四国的相对科研产出在学科之间的分布呈现非均衡态势,在很多学科领域相对产出明显低于世界平均水平;金砖四国22个学科的相对引文影响指标均低于世界平均水平;根据专业化指标值,中国、巴西、印度的学科专业化程度低,俄罗斯的学科专业化程度略高;金砖四国的标准引文影响指标值均明显低于世界平均水平,说明科研论文整体质量低于世界平均水平。据此对金砖四国基础研究建设提出建议,以期为有关部门制定科技发展政策、调整学科结构布局提供参考。  相似文献   
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