Development of LC‐MS/MS method for the determination of dapiprazole on dried blood spots and urine: application to pharmacokinetics

A rapid and highly sensitive liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method for determination of dapiprazole on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse‐phase C₁₈ column (250 × 4.6 mm i.d., 5 µm), using 20 mm ammonium acetate (pH adjusted to 4.0 with acetic acid) and acetonitrile (80:20, v/v) as a mobile phase at 25 °C. LC‐MS detection was performed with selective ion monitoring using target ions at m/z 326 and m/z 306 for dapiprazole and mepiprazole used as internal standard, respectively. The calibration curve showed a good linearity in the concentration range of 1–3000 ng/mL. The effect of hematocrit on extraction of dapiprazole from DBS was evaluated. The mean recoveries of dapiprazole from DBS and urine were 93.88 and 90.29% respectively. The intra‐ and inter‐day precisions were <4.19% in DBS as well as urine. The limits of detection and quantification were 0.30 and 1.10 ng/mL in DBS and 0.45 and 1.50 ng/mL in urine samples, respectively. The method was validated as per US Food and Drug Administration guidelines and successfully applied to a pharmacokinetic study of dapiprazole in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Isolating and Probing the Hot Spot Formed between Two Silver Nanocubes

Out of the frying pan : Hot spots can greatly increase the sensitivity of surface‐enhanced Raman scattering, but they remain poorly understood. A new strategy based on plasma etching (see picture) can be used to isolate and exclusively probe the SERS‐active molecules adsorbed in the hot‐spot region between two silver nanocubes.

     

Fully automated liquid extraction‐based surface sampling and ionization using a chip‐based robotic nanoelectrospray platform

A fully automated liquid extraction‐based surface sampling device utilizing an Advion NanoMate chip‐based infusion nanoelectrospray ionization system is reported. Analyses were enabled for discrete spot sampling by using the Advanced User Interface of the current commercial control software. This software interface provided the parameter control necessary for the NanoMate robotic pipettor to both form and withdraw a liquid microjunction for sampling from a surface. The system was tested with three types of analytically important sample surface types, viz., spotted sample arrays on a MALDI plate, dried blood spots on paper, and whole‐body thin tissue sections from drug dosed mice. The qualitative and quantitative data were consistent with previous studies employing other liquid extraction‐based surface sampling techniques. Published in 2009 by John Wiley & Sons, Ltd.     

基于三维离散元方法研究热点的位置和温度对奥克托今颗粒点火燃烧的影响

炸药的点火燃烧特性与炸药的安全和使用密切相关,其一直是研究者重点关注的问题之一.普遍认为,凝聚炸药起爆的关键是热点.基于此,本文采用三维离散元方法,以奥克托今(HMX)颗粒为研究对象,探究了HMX颗粒中不同位置和初始温度的热点对其燃烧过程的影响.结果发现,热点的不同初始温度和位置都会对HMX炸药颗粒的燃烧特性造成影响.由于处于炸药内部分散位置的热点表面积较大,其相比集中的热点更有利于HMX炸药颗粒的起爆.并且研究发现,并不是热点的温度越高越有利于炸药的起爆,这也取决于炸药颗粒的含量.本文的研究工作对炸药的实验研究以及军事应用提供了一定的参考.     

Hot spot computational identification: Application to the complex formed between the hen egg white lysozyme (HEL) and the antibody HyHEL‐10

The definition and comprehension of the hot spots in an interface is a subject of primary interest for a variety of fields, including structure‐based drug design. Therefore, to achieve an alanine mutagenesis computational approach that is at the same time accurate and predictive, capable of reproducing the experimental mutagenesis values is a major challenge in the computational biochemistry field. Antibody/protein antigen complexes provide one of the greatest models to study protein–protein recognition process because they have three fundamentally features: specificity, high complementary association and a small epitope restricted to the diminutive complementary determining regions (CDR) region, while the remainder of the antibody is largely invariant. Thus, we apply a computational mutational methodological approach to the study of the antigen–antibody complex formed between the hen egg white lysozyme (HEL) and the antibody HyHEL‐10. A critical evaluation that focuses essentially on the limitations and advantages between different computational methods for hot spot determination, as well as between experimental and computational methodological approaches, is presented. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Experimental analysis of interface contact behavior using a novel image processing method

The spatial and temporal evolution of real contact area of contact interface with loads is a challenge. It is generally believed that there is a positive linear correlation between real contact area and normal load. However, with the development of measuring instruments and methods, some scholars have found that the growth rate of real contact area will slow down with the increase of normal load under certain conditions, such as large-scale interface contact with small roughness surface,which is called the nonlinear phenomenon of real contact area. At present, there is no unified conclusion on the explanation of this phenomenon. We set up an experimental apparatus based on the total reflection principle to verify this phenomenon and analyze its mechanism. An image processing method is proposed, which can be used to quantitative analysis micro contact behaviors on macro contact phenomenon. The weighted superposition method is used to identify micro contact spots, to calculate the real contact area, and the color superimposed image is used to identify micro contact behaviors.Based on this method, the spatiotemporal evolution mechanism of real contact area nonlinear phenomena is quantitatively analyzed. Furthermore, the influence of nonlinear phenomenon of real contact area on the whole loading and unloading process is analyzed experimentally. It is found that the effects of fluid between contact interface, normal load amplitude and initial contact state on contact behavior cannot be ignored in large-scale interface contact with small roughness surface.     

A morphological based method to calculate the centroid spots of Hartmann patterns

We have designed a morphological filter in order to calculate the centroid spots of Hartmann patterns. This filter is based on four directional structuring elements. Each element takes into account the general morphology of the spots of the Hartmann pattern. The efficiency of the filter was tested by using a simulated pattern of spots. Finally, we apply this filter to experimental Hartmann patterns obtained for small convex lenses.     

The hot spots conjecture on a class of domains in <Emphasis Type="Italic">R</Emphasis><Superscript><Emphasis Type="Italic">n</Emphasis></Superscript> with <Emphasis Type="Italic">n</Emphasis> ⩾ 3

In this paper, we define a class of domains in R ⁿ . Using the synchronous coupling of reflecting Brownian motion, we obtain the monotonicity property of the solution of the heat equation with the Neumann boundary conditions. We then show that the hot spots conjecture holds for this class of domains.