基于改进排序遗传算法的径向基函数神经网络色谱峰解析

构造了以塔板模型为基函数的径向函数神经网络（P－RBFNN），为了使P－RBFNN具有结构重组能力，又在网络学习算法中引入鲁棒（Rubust)和随机全局最优的两阶段排序遗传算法：结构学习和进化。P－RBFNN结合改进的排序遗传算法很适合组分数未知的色谱（含重叠）峰解析。     

Smoothing and preservation of irregularities using local linear fitting

For nonparametric estimation of a smooth regression function, local linear fitting is a widely-used method. The goal of this paper is to briefly review how to use this method when the unknown curve possibly has some irregularities, such as jumps or peaks, at unknown locations. It is then explained how the same basic method can be used when estimating unsmooth probability densities and conditional variance functions. This research was supported by GOA/07/04-project of the Research Fund KULeuven. Support from the IAP research network nr. P6/03 of the Federal Science Policy, Belgium, is also acknowledged.     

A full-scale tracing study of “ghost peaks” encountered in impurity analysis of budesonide based on experimental operation inspection-liquid chromatography/mass spectrometry fingerprint-mechanism based stress studies integrated strategy

Budesonide is an active pharmaceutical ingredient used in various dosage forms of finished products for the treatment of asthma. During the process of drug development, unbiased analysis of related substances is of utmost significance for both pharmaceutical research and quality control purposes. In this work, the official method documented in the United States Pharmacopoeia was selected to determine the related substances of budesonide considering the pros and cons of critical chromatographic parameters, compared to the European Pharmacopoeia. In doing so, several unpredictable interference peaks, namely “ghost peaks”, were observed occasionally during analysis. A strategy that integrated information derived from experimental operation inspection, liquid chromatography/mass spectrometry fingerprint analysis, and mechanism-based stress studies was then proposed for comprehensively and quickly exploring those non-degradable and degradable peaks. Some ghost peaks were found to originate from nylon syringe filter, illumination, and alkali borosilicate glass high-performance liquid chromatography vials. Besides, degradation pathways under alkaline conditions were also unraveled through liquid chromatography-mass spectrometry qualitative analysis. Overall, an optimization of the analytical methodology based on the United States Pharmacopoeia for its application in impurity analysis of budesonide and corresponding formulations was carried out with the design of experiments, by which “ghost peaks” could be suppressed or prevented. The results obtained herein are not only crucial to studies on budesonide's stability or degradation kinetics but also contribute to clarifying the impurity research of other drugs.     

Use of evaporative light scattering detection for the quality control of drug substances: Influence of different liquid chromatographic and evaporative light scattering detector parameters on the appearance of spike peaks

High performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD) is a versatile, easy to use and inexpensive alternative when it comes to the analysis of substances lacking a chromophor for UV detection. However, in pharmaceutical analysis injection of highly concentrated test solutions are normally required to control impurities at low levels. Under these conditions spike peaks were observed in the chromatograms of the test solutions making a proper evaluation of the impurity profile impossible. The influence of different eluent and ELSD parameters such as eluent composition, eluent flow-rate, ELSD scavenger gas flow-rate and evaporation temperature on the appearance of spike peaks was investigated. It could be shown that spike peaks can be avoided when selecting elevated eluent flow-rates and ESLD scavenger gas flow-rates. Moreover, eluents containing high amounts of organic modifier seem to foster the appearance of spike peaks.     

产学研合作创新方式下政府补贴策略选择

创新补贴策略是政府鼓励企业创新的一种常见政策,考虑到企业内在的吸收能力与外部不同政府补贴策略方式的存在,本文以产学研合作创新方式为基础,通过建立三阶段博弈模型,利用模型解析与仿真分析讨论吸收能力与创新投入分配比例系数对政府补贴策略选择的影响。研究结果表明:无论政府采取哪一种补贴方式,均可以有效激励企业加大创新投入规模,并且企业的吸收能力与R&D投入、产量及社会福利均呈正相关关系;但是,吸收能力对利润及政府补贴的影响受限于补贴方式和企业的创新投入分配比例系数;此外,在创新产品补贴下,创新难度系数对政府补贴额度的影响并不明显,而创新产品补贴总体优于创新投入补贴。     

Occurrence and behavior of system peaks in RP HPLC with solely aqueous mobile phases

System peaks are important but often also disturbing phenomena occurring in separation systems. Behavior of system peaks was studied in reversed phase high performance liquid chromatography (RP HPLC) systems consisting of an RP Amide C16 column and aqueous solutions of organic acids with alkaline metal hydroxides as mobile phases. Binary mobile phases, composed of benzoic acid and lithium hydroxide (LiOH) or cesium hydroxide (CsOH), yielded two system peaks. The first peak was stationary and the second one moved with dilution of the mobile phase or with changes of the alkaline metal hydroxide concentration. The latter changes affected dissociation of the benzoic acid present in the mobile phase and thereby its retention. The presumption that the first system peak is not influenced by the type of alkaline metal cation and that it is related to the non‐adsorbed component of the mobile phase was confirmed by a cyclic procedure. Three‐component mobile phases composed of benzoic acid, tropic acid, and a hydroxide gave rise to three system peaks as expected. The first peak was again stationary and the two others shifted depending on the concentration variation of both acids. Resonance causing a zigzag peak, well described in capillary zone electrophoresis (CZE), was observed if 1‐pentanol was injected into a chromatographic system with one‐component mobile phase.     

神府煤煤岩组分的结构特征及其差异

本文利用ＦＴＩＲ分析及计算、有机溶剂抽提，研究了神府煤不同煤岩组分的结构特征。得出了镜煤的芳构化程度较低，分子中含有较多的烷基侧链及阳离子类基团，而丝炭的芳构化程度较高，分子中含有较多的活性氮。这一结论，对于认识煤岩组分的性质，进行煤岩组分的分离选别有一定的指导意义。     

三元重叠色谱峰面积的定量方法

本从色谱峰的ＥＭＧ模型出发，通过对重叠色谱峰的模拟和回归分析，提出了一种三元重叠色谱峰的面积的定量方法，三元重叠色谱峰的每一个峰面积可以由峰面积比和总面积求得，此法所需的数据都由实验色谱图上测得，峰面积计算结果的相对误差小于±５％，适用于相对峰谷为５０％－９５％的三元重叠色谱峰面积的定量。     

Multiple Peaks in HPLC of Proteins: Bovine Serum Albumin Eluted in a Reversed-Phase System

Elution of a commercial sample of bovine serum albumin (BSA) in a reversed-phase (RP) HPLC system at room temperature gives a distorted peak. If a shallow gradient is used during elution a split peak is observed. The nature of the several parts of this multiple peak is studied using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), amino acid analysis, re-elution in RP-HPLC of collected fractions, capillary electrophoresis (CE), and matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS). This study demonstrates that the split peak of BSA observed in these chromatographic conditions is due to the monomer, dimer and other aggregates existing in the commercial sample of the BSA used. Moreover, it is proved that typical RP-chromatographic conditions do not cause aggregation of BSA.     

直观推导式演进特征投影法对环境样本中多环芳烃的定性定量分析

基于新近发展的直观推导式演进特征投影法(HELP), 本文提出了一个对二维数据进行同时定性定量的分析方法, 并将其成功地用于环境样本中多环芳烃化合物定量解析。对于一维色谱难以定量的重叠峰, HELP方法充分利用色谱、光谱两方面的选择性信息, 得到了具有真实物理意义的唯一解。在定性分辨结果的基础上, 本文还提出了三种可能的定量方法。这种二维数据的解析新方法, 能大幅度地降低对色谱分离条件的要求, 可直接用于复杂实际样本的定性定量分析。