Development and validation of LC–MS/MS method for amlexanox in rat plasma and its application in preclinical pharmacokinetics

Amlexanox, an anti-inflammatory and anti-allergic agent, has been widely used clinically for the treatment of canker sores, asthma, and allergic rhinitis. Recently, amlexanox has received considerable attention in curing nonalcoholic fatty liver diseases and hepatitis virus infection. Herein, we first established a sensitive high-performance liquid chromatography-tandem mass spectrum (LC–MS/MS) method for the determination of amlexanox in rat plasma. Propranolol was used as the internal standard (IS). Using a simple protein precipitation method, the amlexanox and IS were separated with Capcell Pak C18 column (2.0 × 50 mm, 5 μm) and eluted with water and acetonitrile each containing 0.1% formic acid using gradient elution condition at a flow rate of 0.4 mL·min⁻¹. Amlexanox and IS were detected by a triple quadrupole mass in multiple reactive monitoring (MRM) under the transitions of m/z 299.2 → 281.2 and m/z 259.9 → 116.1 with positive electrospray ionization, respectively. The calibration curves of amlexanox were established with the range of 50 to 2000 ng·mL⁻¹ (r² > 0.99). The validation method consisted of selectivity, accuracy, precision, carryover effect, matrix effect, recovery, dilution effect, and stability. The fully validated method was successfully applied to the pharmacokinetic study of amlexanox in Wistar rats.     

Finite-time boundedness of uncertain Hamiltonian systems via sliding mode control approach

Nonlinear Dynamics - This paper seeks to address the problem of finite-time stabilization for a class of uncertain Hamiltonian systems via sliding mode control approach. A novel sliding function in...     

Studies on metabolism of total glucosides of paeony from Paeoniae Radix Alba in rats by UPLC‐Q‐TOF‐MS/MS

Total glucosides of paeony are the active constituents of Paeoniae Radix Alba. In this study, a novel strategy was proposed to find more metabolites and the differences between paeoniflorin, albiflorin and total glucosides of paeony (TGP). This strategy was characterized as follows: firstly, the animals were divided into three groups (paeoniflorin, albiflorin and TGP) to identify the source of TGP metabolites from paeoniflorin or albiflorin; secondly, a generic information‐dependent acquisition scan for the low‐level metabolites was triggered by the multiple mass defect filter and dynamic background subtraction; thirdly, the metabolites were identified with a combination of data‐processing methods including mass defect filtering, neutral loss filtering and product ion filtering; finally, a comparative study was used in the metabolism of paeoniflorin, albiflorin and TGP. Based on the strategy, 18 metabolites of TGP, 10 metabolites of paeoniflorin and 13 metabolites of albiflorin were identified respectively. The results indicated that the hydrolysis, conjugation reaction and oxidization were the major metabolic pathways, and the metabolic sites were the glycosidic linkage, the ester bond and the benzene ring. This study is first to explore the metabolism of TGP, and these findings enhance our understanding of the metabolism and the interactions of paeoniflrin and albiflorin in TGP. Copyright © 2015 John Wiley & Sons, Ltd.     

Dynamic effect of constant inertial acceleration on vibration isolation system with high-order stiffness and Bouc–Wen hysteresis

Nonlinear Dynamics - Nonlinear vibration isolation provides with an effective way for vibration reduction with broad band and high efficiency. This investigation focuses on the dynamic effects of a...     

Heisenberg群上Laplace算子的离散谱

本文证明了Heisenberg群上Laplace算子的Dirichlet特征值的存在性，给出了特征值的估计     

A model study for the steady state error of numerical approximations of inviscid flow equations on Cartesian grid

The widely used locally adaptive Cartesian grid methods involve a series of abruptly refined interfaces. In this paper we consider the influence of the refined interfaces on the steady state errors for second‐order three‐point difference approximations of flow equations. Since the various characteristic components of the Euler equations should behave similarly on such grids with regard to refinement‐induced errors, it is sufficient enough to conduct the analysis on a scalar model problem. The error we consider is a global error, different to local truncation error, and reflects the interaction between multiple interfaces. The steady state error will be compared to the errors on smooth refinement grids and on uniform grids. The conclusion seems to support the numerical findings of Yamaleev and Carpenter (J. Comput. Phys. 2002; 181: 280–316) that refinement does not necessarily reduce the numerical error. Copyright © 2005 John Wiley & Sons, Ltd.     

知识发现中一种变化趋势模型的算法研究

在时序数据库中,有许多成熟的技术和方法用来对布尔型属性之间的关系进行挖掘,但对于数值型属性变化趋势关联关系的研究却不是很多.本文提出了一种数值型属性变化趋势的研究模型QMP(QuantityMovementPattern),依据该模型可利用数据挖掘算法发现不同数值型属性之间变化趋势之间的关系.文中分析了该模型的几种实现算法,并给出了一种快速实现算法及实验数据.     

The Frontier Movement and The American Values and Beliefs

This paper briefly accounts the background of American values and beliefs. It analyses the essence of the American ideals and points out that the American values are exaggerated and glamorized by the American upper class. They are in a sense, a dose of anaesthetic and a kind of hypocrisy.