J. Appl. Cryst.の発刊に際して

Adequate initial configurations for molecular dynamics simulations consist of arrangements of molecules distributed in space in such a way to approximately represent the system's overall structure. In order that the simulations are not disrupted by large van der Waals repulsive interactions, atoms from different molecules must keep safe pairwise distances. Obtaining such a molecular arrangement can be considered a packing problem: Each type molecule must satisfy spatial constraints related to the geometry of the system, and the distance between atoms of different molecules must be greater than some specified tolerance. We have developed a code able to pack millions of atoms, grouped in arbitrarily complex molecules, inside a variety of three-dimensional regions. The regions may be intersections of spheres, ellipses, cylinders, planes, or boxes. The user must provide only the structure of one molecule of each type and the geometrical constraints that each type of molecule must satisfy. Building complex mixtures, interfaces, solvating biomolecules in water, other solvents, or mixtures of solvents, is straightforward. In addition, different atoms belonging to the same molecule may also be restricted to different spatial regions, in such a way that more ordered molecular arrangements can be built, as micelles, lipid double-layers, etc. The packing time for state-of-the-art molecular dynamics systems varies from a few seconds to a few minutes in a personal computer. The input files are simple and currently compatible with PDB, Tinker, Molden, or Moldy coordinate files. The package is distributed as free software and can be downloaded from http://www.ime.unicamp.br/~martinez/packmol/.

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PACKMOL: a package for building initial configurations for molecular dynamics simulations.

基礎講座 電気泳動(Electrophoresis)

It is important that the medical profession plays a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.

Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review …

/pdf/acc-aha-esc-2006-guidelines-for-management-of-patients-with-5a3f1emfzy.pdf

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

The concept of metabolite profiling has been around for decades, but technical innovations are now enabling it to be carried out on a large scale with respect to the number of both metabolites measured and experiments carried out. Here we provide a detailed protocol for gas chromatography mass spectrometry (GC-MS)-based metabolite profiling that offers a good balance of sensitivity and reliability, being considerably more sensitive than NMR and more robust than liquid chromatography-linked mass spectrometry. We summarize all steps from collecting plant material and sample handling to derivatization procedures, instrumentation settings and evaluating the resultant chromatograms. We also define the contribution of GC-MS-based metabolite profiling to the fields of diagnostics, gene annotation and systems biology. Using the protocol described here facilitates routine determination of the relative levels of 300-500 analytes of polar and nonpolar extracts in approximately 400 experimental samples per week per machine.

Gas chromatography mass spectrometry–based metabolite profiling in plants

Several examples of the emergence of unexpected impurities in medicinal products in the past, e.g. the 2018 valsartan scandal, disclosed the need for sophisticated approaches in impurity profiling. Advanced techniques in mass spectrometry offer the possibility to detect impurities in untargeted approaches complementing the targeted search for potential impurities. In this study, a combination of targeted and untargeted approaches using LC-MS/HRMS was applied in creating an impurity profile of bisoprolol fumarate. In the targeted approach, a reaction matrix was used to predict potential impurities, which were searched for in addition to the related substances stated in the European Pharmacopoeia. For the untargeted analytics, general unknown comparative screening was performed to detect unexpected impurities. To cover a maximum range of detectable analytes, two complementary mobile phases, i.e. buffered to acidic and basic pH, were combined with four mass spectrometric ionization conditions, i.e. electrospray ionization and atmospheric pressure chemical ionization in both positive and negative mode. Information-dependent acquisition was used to generate MS and MS/MS data in a single run. The targeted and the untargeted approach revealed the presence of 18 and 17 impurities, respectively. The plausibility of proposed/elucidated structural formulae was checked by in silico fragmentation and assignment of characteristic fragments/neutral losses. Quantification of the impurities was performed with respect to the internal standard metoprolol. The analyzed batches showed contents of up to 0.05% of single impurities. A thorough procedure for the development of a complete impurity profile for drug substances was demonstrated. To ensure a maximum of patient safety, the described approach is prototypical and should be implemented during drug development and after relevant changes in manufacturing processes.

Impurity Profiling of Bisoprolol Fumarate by Liquid Chromatography-High-Resolution Mass Spectrometry: A Combination of Targeted and Untargeted Approaches using a Synthesis Reaction Matrix and General Unknown Comparative Screening

Determination of the Isomeric Composition of Drugs

An die immer schnellere Verbreitung von Methicillin-resistenten Staphylococcus aureus (MRSA) sowohl in Krankenhausern als auch auserhalb haben wir uns in den letzten Jahren gewohnt, obgleich die Behandlung bei Infektion mit diesem gram-positiven Bakterium eine besondere Herausforderung fur den Kliniker ist. In den USA erkranken z.B. ca. 94.000 Menschen jahrlich an MRSA-Infektionen, 19.000 Patienten uberleben die Infektion nicht! Allerdings sind in den letzten Jahren einige Antibiotika auf den Markt gekommen, wie Linezolid oder Tigecylin, bzw. in der Pipeline, die helfen konnen, dass MRSA nicht an Oberhand gewinnt.

Rückkehr in das Vor-Semmelweis-Zeitalter – MRSA, NDM-1 und was kommt noch?

For quality evaluation purposes, a simple, cost-effective, precise, accurate, and rapid planar chromatographic method was developed and validated for the separation of sulfadoxine, sulfalene, and pyrimethamine using standard thin-layer chromatographic plates and a mobile phase consisting of a mixture of toluene, ethyl acetate, and methanol in the ratio 50:28.5:21.5 (% v/v). Densitometric evaluation was carried out by scanning the plates at a wavelength of λ = 254 nm. The method was validated with respect to specificity, linearity, precision, and accuracy. Linearity was proven in a concentration range of 1.00–3.00 μg per spot for sulfalene/sulfadoxine and 0.050–0.150 μg per spot for pyrimethamine with linear regression coefficients (R2) of 0.980–0.990 for all substances. The values for limit of detection (LOD) were 0.107 ng per spot for sulfadoxine, 0.044 ng per spot for sulfalene, and 1.623 ng per spot for pyrimethamine, whereas those for limit of quantification (LOQ) were found to be 0.324 ng per spot fo...

Development and Validation of Simplified High-Performance Thin-Layer Chromatography Densitometric Methods for the Determination of Sulfalene, Sulfadoxine, and Pyrimethamine

Ulrike Holzgrabe

Papers

Impurity Profiling of Bisoprolol Fumarate by Liquid Chromatography-High-Resolution Mass Spectrometry: A Combination of Targeted and Untargeted Approaches using a Synthesis Reaction Matrix and General Unknown Comparative Screening

Determination of the Isomeric Composition of Drugs

Rückkehr in das Vor-Semmelweis-Zeitalter – MRSA, NDM-1 und was kommt noch?

Development and Validation of Simplified High-Performance Thin-Layer Chromatography Densitometric Methods for the Determination of Sulfalene, Sulfadoxine, and Pyrimethamine

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