A simple and reliable stir bar sorptive extraction-liquid chromatography procedure for the determination of chlorpromazine and trifluoperazine in human serum using experimental design methodology

A sensitive and reproducible stir bar sorptive extraction and HPLC-UV detection method was used for the therapeutic drug monitoring of chlorpromazine and trifluoperazine in human serum. The separation was achieved using a C(18) column. The mobile phase consisted of methanol/sodium acetate buffer (pH 4.1; 0.1 M) (95:5, v/v) including 0.5% triethylamine. This miniaturized method can result in faster analysis, lower solvent consumption and less workload per sample while maintaining or even improving sensitivity. In the second part, stir bar sorptive extraction/HPLC-UV method was optimized by a chemometrics approach. An experimental design was therefore used to evaluate the statistically influential and/or interacting factors, among those described in the literature, and to find the best extraction and desorption conditions. Optimal sample volume of 1 mL, extraction time of 24 min at 31°C with pH 8.1 were obtained in a screening 2(5) half fractional factorial design followed by a Box-Behnken design. For the desorption conditions, a Box-Behnken design showed that the best conditions were 150 μL mobile phase for 20 min at 50°C. The optimized method was repeatable (CV<10%, linear (LOQ-500 ng/mL)), with the LOQs equal to 0.7 and 1.5 ng/mL for chlorpromazine and trifluoperazine, respectively.     

Stir bar sorptive extraction for central nervous system drugs from biological fluids

A review with 75 references is presented that deals with the reported methods for analysis of some important central nervous system (CNS) drugs in biological fluids utilizing stir bar sorptive extraction (SBSE) technique covering the years from 2000 to 2008. The theoretical aspects of SBSE, as well as an significant number of applications have been published, showing the advantages of this technique over the classical extraction techniques (liquid–liquid extraction (LLE) and solid-phase extraction (SFE). In this review, recent SBSE developments and a focus on the development of new instrumental approaches and sorbent phases are presented.     

较低应变率大应变条件下聚氨脂泡沫材料的态力学性能实验

利用加长型分离式霍普金森压杆(入射杆长6000mm、子弹长800mm)研究聚氨脂泡沫材料在较 低应变率大应变条件一维应力状态下的动态力学性能,获得了约550s的长加载脉冲,得到了该材料在应变 率520s-1、应变0.15条件下的应力应变曲线,对较低应变率条件下,应变率与动态应力平衡之间的关联进行 了讨论。     

聚苯乙烯混凝土动态劈裂实验

利用直径为74mm 的分离式Hopkinson压杆径向冲击巴西圆盘试样,测试了不同聚苯乙烯(expandedpolystyrene, EPS)颗粒粒径、不同体积含量的EPS混凝土的动态拉伸性能。为了保证实验的可靠性, 在试样和入射杆、透射杆之间加上精确设计的垫块,防止试样两端因应力集中而被压碎破坏;通过选择合适的 整形器,保证试样有足够的时间达到应力均匀。并分析了EPS混凝土劈裂破坏形态。实验结果表明:EPS混 凝土的劈裂强度随应力率的增大而增大;在EPS体积含量较低的EPS混凝土中,EPS混凝土的劈裂强度表 现出一定的粒子尺寸效应,随EPS颗粒体积含量的增加,这一现象逐渐消失。     

Global solution with \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$ \mathcal {C}^{k}$\end{document}‐estimates for \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\bar{\partial }$\end{document}‐equation on q‐convex intersections

We construct a global solution with $\mathcal {C}^{k}$‐estimates for the $\bar{\partial }$‐equation on q‐convex intersections.     

Efficient inclusion of receptor flexibility in grid-based protein-ligand docking

Accounting for receptor flexibility is an essential component of successful protein-ligand docking but still marks a major computational challenge. For many target molecules of pharmaceutical relevance, global backbone conformational changes are relevant during the ligand binding process. However, popular methods that represent the protein receptor molecule as a potential grid typically assume a rigid receptor structure during ligand-receptor docking. A new approach has been developed that combines inclusion of global receptor flexibility with the efficient potential grid representation of the receptor molecule. This is achieved using interpolation between grid representations of the receptor protein deformed in selected collective degrees of freedom. The method was tested on the docking of three ligands to apo protein kinase A (PKA), an enzyme that undergoes global structural changes upon inhibitor binding. Structural variants of PKA were generated along the softest normal mode of an elastic network representation of apo PKA. Inclusion of receptor deformability during docking resulted in a significantly improved docking performance compared with rigid PKA docking, thus allowing for systematic virtual screening applications at small additional computational cost.     

Determination of parabens in house dust by pressurised hot water extraction followed by stir bar sorptive extraction and thermal desorption-gas chromatography-mass spectrometry

This study describes the development of a new method for determining p-hydroxybenzoic esters (parabens) in house dust. This optimised method was based on the pressurised hot water extraction (PHWE) of house dust, followed by the acetylation of the extracted parabens, stir bar sorptive extraction (SBSE) with a polydimethylsiloxane stir bar, and finally analysis using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). The combination of SBSE and PHWE allows the analytes to be preconcentrated and extracted from the aqueous extract in a single step with minimal manipulation of the sample. Furthermore the in situ acetylation of parabens prior to SBSE improved their extraction efficiency and their GC-MS signal. The method showed recoveries of between 40 and 80%, good linearity, repeatability and reproducibility (<10% RSD, at 100 ng g(-1), n=5), low limits of detection (from 1.0 ng g(-1) for propyl paraben to 2.1 ng g(-1) for methyl paraben) and quantification (from 3.3 ng g(-1) for propyl paraben to 8.5 ng g(-1) for methyl paraben). The proposed method was applied to the analysis of house dust samples. All the target parabens were found in the samples. Methyl and propyl parabens were the most abundant, with concentrations up to 2440 ng g(-1) and 910 ng g(-1), respectively. The high levels of parabens found in the samples confirm the importance of determining organic contaminants in indoor environments.     

Rapid and selective determination of UV filters in seawater by liquid chromatography-tandem mass spectrometry combined with stir bar sorptive extraction

Fast liquid chromatography coupled to triple-quadrupole tandem mass spectrometry was employed for the determination of six UV filters in seawater. The separation of the analytes was achieved in less than 5 min; polarity switching was used as four of the analytes were ionized in positive mode and the remaining two in negative mode. Two ionization sources were employed and compared: atmospheric pressure chemical ionization (APCI) gave better results than electrospray ionization (ESI) for all analytes, with higher reproducibility and lower detection limits. Therefore APCI was chosen for the determination of the analytes in seawater samples using stir bar sorptive extraction-liquid desorption (SBSE-LD).Quantitative analysis was performed in multiple reaction monitoring (MRM) mode; fragmentation pathways of the analytes with regard to the formation of the MRM ions were also proposed.For the analysis of seawater samples, calibration curves were drawn using SBSE in spiked seawater. All figures of merit of the method were satisfactory; limits of detection were particularly low for the four analytes ionized in positive mode, being in the range 8-31 ng/L. The method was applied to the determination of the six UV filters in seawater samples from Liguria, Italy. Only benzophenone-3 (BP-3) and ethylhexyl methoxycinnamate (EHMC) were measured in the analyzed samples; some of the remaining analytes were also detected but always below the limit of quantitation.     

Integrating effective flexibility measures into a strategic supply chain planning model

This paper develops models for capacity, product mix, distribution and input supply flexibility and integrates them in a strategic level, mixed integer supply chain (SC) planning model as a way of addressing demand and supply uncertainty, as well as improving market responsiveness. Capacity flexibility is modeled via the SC’s production capacity planning to address budgeted demand and ensure the fulfillment of prospective demand increases when considering various market scenarios. This model selects an optimal number of products from fast moving and extended product range options—based on the product mix flexibility. The model confirms a quick response to a changing marketplace by considering elements like transportation and supply lead time along with the probabilities of stock out options when addressing input supply and distribution flexibility. This paper proposes a solution procedure to solve the model for real world problems, and investigates the sensitivity of the model outputs with respect to changes in flexibility measures.     

技术柔性、柔性生产与柔性技术的价值

在产品市场和要素市场存在不确定性的条件下,将企业的生产行为和技术柔性水平的选择纳入一个统一框架进行分析,给出了柔性技术的价值函数及其特征.结果表明,给定技术柔性水平,柔性生产行为价值不会低于非柔性生产行为的价值;给定生产行为,柔性技术的价值不会随着其柔性增加而降低.进一步,在一定条件下,柔性生产行为比非柔性生产行为更具价值,柔性技术的价值随着其柔性水平的增加而增加.