Quantification of midazolam,morphine and metabolites in plasma using 96‐well solid‐phase extraction and ultra‐performance liquid chromatography–tandem mass spectrometry

Currently, pharmacokinetic–pharmacodynamic studies of sedatives and analgesics are performed in neonates and children to find suitable dose regimens. As a result, sensitive assays using only small volumes of blood are necessary to determine drug and metabolite concentrations. We developed an ultra‐performance liquid chromatographic method with tandem mass spectrometry detection for quantification of midazolam, 1‐hydroxymidazolam, hydroxymidazolamglucuronide, morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide in 100 μL of plasma. Cleanup consisted of 96 wells micro‐solid phase extraction, before reversed‐phase chromatographic separation (ultra‐performance liquid chromatography) and selective detection using electrospray ionization tandem mass spectrometry. Separate solid‐phase extraction methods were necessary to quantify morphine, midazolam and their metabolites because of each group's physicochemical properties. Standard curves were linear over a large dynamic range with adequate limits of quantitation. Intra‐ and interrun accuracy and precision were within 85–115% (of nominal concentration using a fresh calibration curve) and 15% (coefficient of variation, CV) respectively. Recoveries were >80% for all analytes, with interbatch CVs (as a measure of matrix effects) of less than 15% over six batches of plasma. Stability in plasma and extracts was sufficient, allowing large autosampler loads. Runtime was 3.00 min per sample for each method. The combination of 96‐well micro‐SPE and UPLC‐MS/MS allows reliable quantification of morphine, midazolam and their major metabolites in 100 μL of plasma. Copyright © 2010 John Wiley & Sons, Ltd.     

Maximum feasibility guideline in the design and analysis of protein folding potentials

Protein folding potentials are expected to have the lowest energy for the native shape. The Linear Programming (LP) approach achieves exactly that goal for a training set, or indicates that this goal is impossible to obtain. If a solution cannot be found (i.e., the problem is infeasible) two possible routes are possible: (a) choosing a new functional form for the potential, (b) finding the best potential with a feasible subset of the data, and (or) detecting inconsistent subset of the data in the training set. Here, we explore option (b). A simple heuristic for finding an approximate solution to an infeasible set of linear inequalities is outlined. An approximately feasible solution is obtained iteratively, starting from a certain initial guess, by computing a series of analytic centers of the polyhedra defined by all the inequalities satisfied at the subsequent iterations. Standard interior point algorithms for Linear Programming can be used to compute efficiently the analytic center of a polyhedron. We demonstrate how this procedure can be used for the design of folding potentials that are linear in their parameters. The procedure shows an improvement in the quality of the potentials and sometimes points to flaws in the original data.     

Inverse Monte Carlo renormalization group transformations for critical phenomena

We introduce a computationally stable inverse Monte Carlo renormalization group transformation method that provides a number of advantages for the calculation of critical properties. We are able to simulate the fixed point of a renormalization group for arbitrarily large lattices without critical slowing down. The log-log scaling plots obtained with this method show remarkable linearity, leading to accurate estimates for critical exponents. We illustrate this method with calculations in two- and three-dimensional Ising models for a variety of renormalization group transformations.     

Density-fluctuation-induced swelling of polymer thin films in carbon dioxide

We report an anomalous swelling of polymer thin films in carbon dioxide (CO(2)) which is associated (in both locus and form) with the density fluctuation ridge that forms along the extension of the coexistence curve of gas and liquid in the P-T phase diagram. Neutron reflectivity results showed that CO(2) could be sorbed to a large extent ( approximately 60%) in thin polymer films even when the bulk miscibility of the polymer with CO(2) is very poor. The anomalous swelling is found to scale with the polymer radius of gyration (R(g)) and extends to a distance approximately 10 R(g).     

Fluorescence spectra of matrix-isolated praseodymium triodide molecules

Fluorescence spectra of PrI₃ molecules isolated in Ar and Xe matrices have been measured for the first time. More than 40 transitions have been measured using Hg excitation and have been assigned to transitions within the 4f² configuration.     

The German bakery waste incident; use of a combined approach of screening and confirmation for dioxins in feed and food

During the last six years several incidents have occurred with dioxins in feed, stressing the need for rapid screening methods for these compounds. The most recent incident was the contamination of bakery waste used for animal feed due to the use of waste wood for drying of the material. In addition to Germany, the material was also shipped to the Netherlands. Levels up to 12 ng TEQ/kg have been detected, being about 15 times over the current limit of 0.75 ng TEQ/kg. In the Netherlands a combined strategy of screening with the CALUX-bioassay and the HRGC/HRMS confirmatory method was used to rapidly control the incident. Pigs were contaminated by the incident but only to a very limited extent. Despite the rather low limits for pig meat, the CALUX bioassay showed excellent performance, once again confirming the value of this assay.     

Bosons as the origin for giant magnetic properties of organic monolayers

Recently, unusual giant magnetic properties were found experimentally in some organized organic monolayers adsorbed on solid substrates. A model is presented which explains the observed phenomenon. The model is based on the special properties of electrons transferred from the substrate to the layer as a result of the adsorption process. Triplet pairing of those electrons is forced by the special 2D properties of the organic layer. Such pairs are confined within domains in the organic layer and their quantum statistics provide a model that explains the unique magnetization as well as all other features of the experimental observations. The model suggests the possible existence of Bose-Einstein condensation at room temperature on the scale of the domains.