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.     

Global existence and time decay of the non-cutoff Boltzmann equation with hard potential

This paper is concerned with the Cauchy problem on the Boltzmann equation without angular cutoff assumption for hard potential in the whole space. When the initial data is a small perturbation of a global Maxwellian, the global existence of solution to this problem is proved in unweighted Sobolev spaces $H^N\left({\mathbb{R}}_{x,v}^6\right)$ with $N\ge 2$. But if we want to obtain the optimal temporal decay estimates, we need to add the velocity weight function, in this case the global existence and the optimal temporal decay estimate of the Boltzmann equation are all established. Meanwhile, we further gain a more accurate energy estimate, which can guarantee the validity of the assumption in Chen et al. (0000).     

基于混合优化算法的关节臂式测量机参数标定

为进一步提高关节臂式坐标测量机等高机动性精密测量设备的测量精度,使用D-H矩阵法建立其关节坐标转换数学模型并据此推导出参数误差模型.针对非线性多参数标定问题,通过变换分析消除了最小二乘法求解时矩阵中的冗余参数,降低了计算的复杂性.设定判定准则并实现最小二乘法和模拟退火算法的混合,提出了一种基于混合优化算法的参数标定方法,解决了LM算法的初值设定和SA算法的搜索效率逐步降低的问题.实验结果表明:关节臂式测量机参数经混合优化算法标定后,参数的误差范围有了显著的缩小,单点重复性误差的平均值减小了1.746 mm,长度误差的平均值减小了0.941 mm,测量误差得到了进一步的抑制.     

轧制道次间插入冷却对特厚钢板组织与性能的影响

使用实验轧机旁冷却装置配合轧机进行轧制实验，研究轧制道次间不同冷却工艺对特厚钢板组织和性能的影响规律.研究结果表明:采用道次间冷却工艺可以在全厚度方向获得组织细化及强韧性提高效果，采用强冷道次间冷却实验钢1/4处晶粒尺寸可细化至10μm，强度为376MPa，-40℃冲击功为169J;心部晶粒尺寸可细化至15μm，强度为360MPa，-40℃冲击功为123J.本工艺可形成470μm厚表层细晶层，晶粒尺寸可细化至5μm;粗轧道次间插入冷却工艺轧制钢板强度和冲击韧性优于中间坯冷却工艺;随冷却强度增加，钢板内部组织明显细化且强度大幅提高.     

高陡横坡段桩柱式桥梁双桩基础受力分析

基于高陡横坡段桩柱式桥梁双桩基础承载特性,提出了一种改进有限杆单元计算分析方法.分析了高陡横坡段桩柱式桥梁双桩基础承载机理及受力特性,建立了双桩基础计算分析模型.其次,根据前、后桩与边坡相对位置关系,给出了后桩所受剩余下滑力与前桩所受土压力的比例关系.在传统有限杆单元分析方法基础上,结合陡坡桩受力特征,导得了考虑桩土共同作用与"P-Δ"效应的单元刚度矩阵修正方法,并在此基础上编制了适用于高陡横坡段桩柱式桥梁双桩基础的有限杆单元分析MATLAB计算程序.采用室内模型试验对本文计算方法进行验证,给出了适用于陡坡段桥梁桩基的设计流程图.研究结果表明:本文理论计算值与模型试验实测结果吻合良好,表明本文计算方法正确可行,可为同类工程设计提供参考.     

基于LQG控制的整车8-DOF系统振动分析

建立了整车8-DOF系统动力学模型,考虑了主动悬架控制,并增设了主动座椅控制,设计了车辆主动悬架系统的LQG控制器。基于Matlab仿真平台建立了整车8-DOF系统动力学仿真模型,对所得最优控制策略下的动态响应进行了仿真验证。仿真结果表明:为了改善人椅系统质心及车身质心的跳振性能需要在一定程度上弱化各轮轮胎动位移性能。从控制效能上来看,该最优控制器能够满足各行驶状态下对悬架性能的要求,改善了车辆的行驶平顺性。     

疏松砂岩油藏大孔道定性识别新方法研究

疏松砂岩油藏在长期注水开发过程中,往往伴随着大孔道的出现,这严重影响了油藏水驱开发效果,制约了采出程度的进一步提高,因此,大孔道识别及有效封堵成为该类油藏急需解决的关键问题.通过研究分析,确定了影响大孔道从形成到发展的7种主要静态因素,以及标志大孔道形成的6种主要动态因素.将层次分析法及灰色关联法相结合,分别计算静态及动态因素的权重,建立了全新的大孔道定性识别模型.示踪剂监测结果验证了该方法的实用性和有效性.     

Synthesis,spectral investigation and development of tetrahedral copper(II) complexes as artificial metallonucleases and antimalarial agents

Seven new copper(II) complexes of type [Cu(A)(L)]?H₂O (A = sparfloxacin, ciprofloxacin, levofloxacin, gatifloxacin, pefloxacin, ofloxacin, norfloxacin; L = 5‐[(3‐chlorophenyl)diazenyl]‐4‐hydroxy‐1,3‐thiazole‐2(3H)‐thione) were synthesized and characterized using elemental and thermogravimetric analyses, and electronic, electron paramagnetic resonance (EPR), Fourier transform infrared and liquid chromatography–mass spectroscopies. Tetrahedral geometry around copper is assigned in all complexes using EPR and electronic spectral analyses. All complexes were investigated for their interaction with herring sperm DNA utilizing absorption titration (K_b = 1.27–3.13 × 10⁵ M^?1) and hydrodynamic volume measurement studies. The studies suggest the classical intercalative mode of DNA binding. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The results indicate that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA. The superoxide dismutase mimic activity of the complexes was evaluated by nitroblue tetrazolium assay, and the complexes catalysed the dismutation of superoxide at pH = 7.8 with IC₅₀ values in the range 0.597–0.900 μM. The complexes were screened for their in vitro antibacterial activity against five pathogenic bacteria. All the complexes are good cytotoxic agents and show LC₅₀ values ranging from 5.559 to 11.912 µg ml^?1. All newly synthesized Cu(II) complexes were also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain (IC₅₀ = 0.62–2.0 µg ml^?1). Copyright © 2015 John Wiley & Sons, Ltd.