Efficient and selective analytical method for the quantification of a β-adrenoceptor agonist,isoproterenol, by LC–MS/MS and its application to pharmacokinetics studies

Isoproterenol (ISO) is a synthetic catecholamine with a powerful cardiac stimulate, bronchial smooth and skeletal muscle relaxation, coronary artery and peripheral vasodilator effects. In this study, a simple, rapid, and selective liquid chromatography–tandem mass spectrometry has been developed for the determination of ISO in rat plasma. Proteins were precipitated in plasma samples with 0.1?g?mL^?1 trichloroacetic acid and the ISO/internal standard (IS) were separated on a C₈ column. The ISO was detected by a triple-quadrupole mass spectrometer with electrospray ionization source. The transitions of m/z 212.1?→?193.9 for ISO and m/z 285.2?→?193.2 for IS were conducted through multiple reaction monitoring mode. This method was linear over the range of 2–500?n?g?mL^?1. The intra- and inter-day assay precision were observed between 3 and 10%. The accuracy was within ±11%. Stability study results demonstrated that ISO was stable in the autosampler at 4°C for 24?hr, and for 8?hr at room temperature. Only one freeze–thaw cycle at ?80°C for 24?hr was found to be stable. The validated method was successfully applied to a pharmacokinetic study of ISO in rats following subcutaneous administration.     

JP-10裂解的激波管实验与动力学模拟

利用单脉冲激波管对碳氢燃料JP-10在1150~1300K条件下的高温热裂解特性进行了实验研究,采用气相色谱法分析热裂解产物并获得了热裂解速率系数.主要裂解产物有乙烯、乙炔、丙烯、丁烯、1,3-丁二烯、环戊二烯、环戊烯、苯、甲苯,以及少量的甲烷、乙烷、二甲苯和甲基环戊烯.将每次激波管实验后所有产物浓度累加, JP-10裂解速率系数由实验测定.为了消除激波运行中非理想性和边界层效应导致反应温度确定的误差,采用对比速率法确定裂解温度,即在反应物中加入少量热解速率已知的内标物,根据内标物在相同的激波管实验条件下的裂解程度确定反应温度.根据内标物裂解量确定的激波管裂解反应温度通常小于采用传统测量激波速度由激波关系计算的反射激波后5区温度.在1200~1300K之间两种方法得到的温度吻合得较好,差异在20K以内,随着温度升高,两者差异增大.在实验研究的基础上,依据San Diego Mechanism对JP-10高温裂解过程进行了动力学模拟.结果显示:主要裂解产物中乙烯、乙炔和1,3-丁二烯产量随温度变化的实验值与San Diego Mechanism的模拟结果有很好的一致性,但环戊烯产量的实验值比模拟值高很多,预示JP-10裂解中完全开环和部分开环反应都是重要的裂解通道.      

多重分形降趋波动分析法和移动平均法的分形谱算法对比分析

多重分形降趋波动分析法(MFDFA)和多重分形降趋移动平均法(MFDMA)是用来估算一维随机分形信号多重分形谱的两种算法, 已被拓展应用于二维和高维分形信号的分析. 本文简要介绍了MFDFA和MFDMA算法及其在一维时间序列中的应用. 首次系统地从算法模型、计算统计精度、样本量的敏感性、无标度区选取的敏感性、矩选择的敏感性和计算量这六个方面对两种算法进行了对比分析, 以典型多重分形信号BMC信号为例, 分析两种算法的适用性和优劣性. 为实际应用中, 针对具体信号如何选用MFDFA或MFDMA算法, 以及两种算法的参数设置提供了有价值的参考.     

Determination of azasetron hydrochloride in rabbit plasma by liquid chromatography tandem mass spectrometry and its application

A sensitive and selective liquid chromatography tandem mass spectrometry method for determination of azasetron hydrochloride in rabbit plasma was developed. After addition of doxapram hydrochloride as internal standard (IS), protein precipitation by 10% trichloroacetic acid was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C(18) (2.1 × 50 mm, 3.5 μm) column with acetonitrile-water as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring mode was used to quantification using target fragment ions m/z 349.9 → 223.5 for azasetron hydrochloride and m/z 378.9 → 291.8 for the IS. Calibration plots were linear over the range of 6-1000 ng/mL for azasetron hydrochloride in plasma. The lower limit of quantitation for azasetron hydrochloride was 6 ng/mL. The mean recovery of azasetron hydrochloride from plasma was in the range 85.6-92.7%. The RSDs of intra-day and inter-day precision were both less than 12%. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of azasetron hydrochloride in rabbit plasma.     

Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel inhibitor of angiogenesis E-3810 in human plasma and its application in a clinical pharmacokinetic study

E-3810, 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolyl]oxy]-N-methyl-naphthalene-1-carboxamide, is a novel, potent, dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors with antiangiogenic properties, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to measure the drug in human plasma on the basis of simple protein precipitation with methanol after addition of deuterated E-3810 as internal standard. The method requires a small volume of sample (100 μl) and is rapid and selective, allowing good resolution of peaks in 5 min. It is sensitive, precise, and accurate, with overall precision, expressed as CV%, always ≤7.1%, accuracy in the range 92.7%-104.4%, and high recovery, close to 100%. The limit of detection is 0.01 ng/ml, and the lower limit of quantitation is 2.0 ng/ml. The assay was validated in the range from the lower limit of quantitation up to 500.0 ng/ml. This is the first method developed and validated for analyzing E-3810 in human plasma. The method has been successfully applied to study E-3810 pharmacokinetics in cancer patients with solid tumors who are receiving daily oral doses of the drug during the phase I trial.     

In vivo solid-phase microextraction for single rodent pharmacokinetics studies of carbamazepine and carbamazepine-10,11-epoxide in mice

The use of solid-phase microextraction (SPME) for in vivo sampling of drugs and metabolites in the bloodstream of freely moving animals eliminates the need for blood withdrawal in order to generate pharmacokinetics (PK) profiles in support of pharmaceutical drug discovery studies. In this study, SPME was applied for in vivo sampling in mice for the first time and enables the use of a single animal to construct the entire PK profile. In vivo SPME sampling procedure used commercial prototype single-use in vivo SPME probes with a biocompatible extractive coating and a polyurethane sampling interface designed to facilitate repeated sampling from the same animal. Pre-equilibrium in vivo SPME sampling, kinetic on-fibre standardization calibration and liquid chromatography–tandem mass spectrometry analysis (LC–MS/MS) were used to determine unbound and total circulating concentrations of carbamazepine (CBZ) and its active metabolite carbamazepine-10,11-epoxide (CBZEP) in mice (n = 7) after 2 mg/kg intravenous dosing. The method was linear in the range of 1–2000 ng/mL CBZ in whole blood with acceptable accuracy (93–97%) and precision (<17% RSD). The single dose PK results obtained using in vivo SPME sampling compare well to results obtained by serial automated blood sampling as well as by the more conventional method of terminal blood collection from multiple animals/time point. In vivo SPME offers the advantages of serial and repeated sampling from the same animal, speed, improved sample clean-up, decreased animal use and the ability to obtain both free and total drug concentrations from the same experiment.     

1996～2000年《武汉大学学报(自然科学版)》引文分析

以1996-2000年《武汉大学学报（自然科学版）》上发表的917篇科技论文为统计样本，据义献计量学的方法对其引文进行了统计分析．结果表明：《武汉大学学报（自然科学版）》篇均引文节为7．83，引文主要类型为期刊。占76．6％。外文文献占引文总数的66．77％，最大中文引文年限为2年，半哀期为7年，衰减系数为31．30％．最大外义引文年限为3年，半哀期为10年，哀减系数为17．08％．刊载论文的总被引量和总影响因子在逐年增加。     

基于产业聚集的城镇化发展战略研究--对安徽省地级城市发展的思考

本文运用2000年至2003安徽省17个城市的统计资料，运用比较分析法和回归分析法，从城市规模、产业聚集、要素聚集以及综合经济实力等方面，对安徽省17个地级城市的发展进行了分析。主要结论认为，近几年来安徽省城市化发展步伐加快，城市规模、产业聚集与城市综合经济实力三者关系密不可分。但安徽省在城市化过程中存在着城市空间规模外延式扩张多，注重城市内涵效益的发展不够的问题，而城市发展的首要任务是产业的发展，带动要素的聚集，进而促进城市化水平的提高。安徽省城市发展的关键是建立有利于城市化发展的聚集机制和政策环境。     

不确定条件下多属性决策的比较因素法(英文)

本文针对不确定条件下多属性决策问题,扩展了原有多属性决策的概念,引入了比较因素与次比较因素,获得了其一些代数性质以及相应的定理。在此基础上,给出了不确定条件下多属性决策的比较因素法。     

长沙建设国家中心城市的对策研究

建设国家中心城市是长沙市近年的奋斗目标.长沙市怎样建设国家中心城市,可以从与国内其他国家中心城市的全面比照当中得到建设方案.一是从经济实力、产业结构、科教实力、金融行业发展、对外开放等代表城市综合实力的5个方面,二是从引领和辐射功能、集聚功能、物流枢纽功能等代表城市功能的3个方面,对长沙与国内5个国家中心城市(天津、重庆、成都、武汉、郑州)进行对比研究.通过对比,从国内5个国家中心城市的城市功能差别当中找准长沙的城市功能定位,从长沙市城市综合实力的差距和优劣势当中发现长沙建设国家中心城市所要解决的问题,为此提出长沙建设国家中心城市的建设对策.