Purification of drugs from biological fluids by counter-current chromatography

Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR.     

PhAST: pharmacophore alignment search tool

We present a ligand-based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text-based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand-based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5-lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence-based compound screening with substantial scaffold hopping potential.     

Design of compound libraries for fragment screening

Approaches to the design of libraries for fragment screening are illustrated with reference to a 20 k generic fragment screening library and a 1.2 k generic NMR screening library. Tools and methods for library design that have been developed within AstraZeneca are described, including Foyfi fingerprints and the Flush program for neighborhood characterization. It will be shown how Flush and the BigPicker, which selects maximally diverse sets of compounds, are used to apply the Core and Layer method for library design. Approaches to partitioning libraries into cocktails are also described.     

荧光分析法测定荜茇有效成分荜茇宁

根据荜茇有效成分荜茇宁的荧光被表面活性剂OP-10显著增敏的特征,提出了胶束增敏荧光法测定蒙药荜茇中荜茇宁的荧光分析新方法.荜茇宁的含量在2.0～16.0μg/mL范围内,与其荧光强度呈良好的线性关系,相关系数为0.9992,方法的回收率为96.9%～104.5%.此方法适合蒙药荜茇中荜茇宁的测定.     

Distant collaboration in drug discovery: the LINK3D project

The work describes the development of novel software supporting synchronous distant collaboration between scientists involved in drug discovery and development projects. The program allows to visualize and share data as well as to interact in real time using standard intranets and Internet resources. Direct visualization of 2D and 3D molecular structures is supported and original tools for facilitating remote discussion have been integrated. The software is multiplatform (MS-Windows, SGI-IRIX, Linux), allowing for a seamless integration of heterogeneous working environments. The project aims to support collaboration both within and between academic and industrial institutions. Since confidentiality is very important in some scenarios, special attention has been paid to security aspects. The article presents the research carried out to gather the requirements of collaborative software in the field of drug discovery and development and describes the features of the first fully functional prototype obtained. Real-world testing activities carried out on this prototype in order to guarantee its adequacy in diverse environments are also described and discussed.In addition to the mentioned institutions the LINK3D Consortium is constituted by     

Addition of modifier in supercritical fluid chromatography using a microbore reciprocating pump

Summary Solubilities of polar analytes in supercritical CO₂ can be enhanced by the addition of polar modifiers. The addition of modifier into an SFC system using a low cost reciprocating pump has been studied. Two different mixing chambers were evaluated for mixing the supercritical CO₂ with modifier. It appeared that a mixing chamber with a packed bed was enough to reduce baseline noise from the modifier pump. Results from the effect of pressure and temperature with various modifier flow rates were obtained. High percentages of modifier (>15%) at a low CO₂ pressure (2000 psi) caused baseline instability. In addition, different I.D. columns were tested with the system and the effect of modifier compressiblity on detector noise was also studied. Several pharmaceutical compounds were separated to demonstrate system performance.     

Analysis of diastereoisomer impurities in chiral pharmaceutical compounds by capillary electrophoresis

Summary Micellar electrokinetic capillary chromatography (MECC) has been applied to the separation and analysis of diastereoisomer impurities in chiral pharmaceutical compounds. Differences in separation mechanism and selectivity make MECC useful as an alternative method to HPLC for analysis of these synthetic inpurities. Advantages of MECC include high efficiency separations and low consumption of sample and solvents. Water soluble and insoluble pharmaceutical compounds are used to illustrate the separation characteristics and quantitative capabilities of this versatile new analytical technique.     

原子吸收光谱法间接测定硫酸阿托品

研究了原子吸收光谱法间接测定硫酸阿托品的方法。在pH为5．0的溶液中，当四苯硼钠过量时可完全沉淀硫酸阿托品，在滤液中加入过量的氯化钾沉淀剩余的四苯硼钠，再测定过量的钾可以计算得到硫酸阿托品的含量。方法简单、快速，回收率在97％－101％之间，相对标准偏差为1．1％。     

The Discovery of the Tau Lepton and the Changes in Elementary-Particle Physics in Forty Years

I describe the discovery of the tau lepton in the 1970s using the SPEAR electron-positron collider and the SLAC-LBL detector of the Stanford Linear Accelerator Center. I also describe the subsequent verification of the existence of the tau lepton and its leptonic nature by experiments at SPEAR and at the DORIS electron-positron collider at DESY. As a preliminary to the tau discovery I discuss how I became a physicist and became interested in leptons. This history of the discovery of the tau allows me to give a general picture of the high-energy physics world of forty years ago and to discuss the changes that have occurred in the practice of high-energy physics over these forty years.Martin L. Perl is a professor, experimenter, and group leader at the Stanford Linear Accelerator Center of Stanford University. In 1995 he was awarded the Nobel Prize in Physics for his discovery of the tau lepton.