Preparation of 3-azetidinols with non-bulky 1-alkyl substituents

Cyclization of either the tetrahydropyranyl or trimethylsilyl ether of 1-(alkylamino)-3-chloro-2-propanols 1 followed by cleavage of the azetidinyl ether provides a general method for the preparation of 1-alkyl-3-azetidinols. Unhindered amines provide a more facile preparation of derivatives of 1 , or its ethers, than do hindered amines, while hindered derivatives of 1 undergo more facile ring closure.     

Simulations of radiative effects on the Rayleigh–Taylor instability using the CRASH code

Future experiments at the National Ignition Facility will be able to generate diagnosable Rayleigh–Taylor instability growth in the presence of locally generated, high radiation fluxes. This interplay of radiative energy transfer and hydrodynamic instability is relevant to many astrophysical systems, such as core-collapse red supergiant supernovae. Previous simulations of high-energy-density Rayleigh–Taylor instabilities in the presence of a hot environment near a radiative shock demonstrate behavior that differs from that found in non-radiative cases. However, these simulations considered only 1D or single wavelength cases. Here we report simulations of an entire experimental system using the CRASH code. These simulations lead to modified predictions, attributed to the effects of radial energy losses.     

Analysis of volatile organic compounds released from the decay of surrogate human models simulating victims of collapsed buildings by thermal desorption–comprehensive two-dimensional gas chromatography–time of flight mass spectrometry

Field experiments were devised to mimic the entrapment conditions under the rubble of collapsed buildings aiming to investigate the evolution of volatile organic compounds (VOCs) during the early dead body decomposition stage. Three pig carcasses were placed inside concrete tunnels of a search and rescue (SAR) operational field terrain for simulating the entrapment environment after a building collapse. The experimental campaign employed both laboratory and on-site analytical methods running in parallel. The current work focuses only on the results of the laboratory method using thermal desorption coupled to comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (TD-GC × GC-TOF MS). The flow-modulated TD-GC × GC-TOF MS provided enhanced separation of the VOC profile and served as a reference method for the evaluation of the on-site analytical methods in the current experimental campaign. Bespoke software was used to deconvolve the VOC profile to extract as much information as possible into peak lists. In total, 288 unique VOCs were identified (i.e., not found in blank samples). The majority were aliphatics (172), aromatics (25) and nitrogen compounds (19), followed by ketones (17), esters (13), alcohols (12), aldehydes (11), sulfur (9), miscellaneous (8) and acid compounds (2). The TD-GC × GC-TOF MS proved to be a sensitive and powerful system for resolving the chemical puzzle of above-ground “scent of death”.     

Dual‐Modal Magnetic Resonance/Fluorescent Zinc Probes for Pancreatic β‐Cell Mass Imaging

Despite the contribution of changes in pancreatic β‐cell mass to the development of all forms of diabetes mellitus, few robust approaches currently exist to monitor these changes prospectively in vivo. Although magnetic‐resonance imaging (MRI) provides a potentially useful technique, targeting MRI‐active probes to the β cell has proved challenging. Zinc ions are highly concentrated in the secretory granule, but they are relatively less abundant in the exocrine pancreas and in other tissues. We have therefore developed functional dual‐modal probes based on transition‐metal chelates capable of binding zinc. The first of these, Gd ?1 , binds Zn^II directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from λ_em=410 to 500 nm with an increase in relaxivity from r₁=4.2 up to 4.9 mM ^?1 s^?1. The probe is efficiently accumulated into secretory granules in β‐cell‐derived lines and isolated islets, but more poorly by non‐endocrine cells, and leads to a reduction in T₁ in human islets. In vivo murine studies of Gd ?1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes.     

A fully validated method for the determination of vardenafil in blood using gas chromatography/mass spectrometry

Vardenafil (VDN) is one of the three commercially available phosphodiesterase type 5 inhibitors and it is mainly used in the treatment of erectile dysfunction. A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method for the determination of VDN in blood has been developed and validated. Sample preparation included solid-phase extraction and derivatization with N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA) and 1% tert-butyldimethylsilylchloride (TBDMSCl). Protriptyline was used as the internal standard for this assay. Limits of detection and quantification for VDN were 0.70 and 2.00 μg/l, respectively. The calibration curves were linear within the dynamic range 2.00-200.0 μg/l with a correlation coefficient higher than 0.991. Absolute recovery ranged from 88.6% to 95.7% for the analyte of interest at three quality control levels. Intra- and inter-day accuracy was found to be between - 6.1% to 10.8% and - 9.3% to 11.6%, respectively, whereas intra- and inter-day precision was < 7.8% and 9.7%, correspondingly. The proposed method is the first fully validated GC/MS method for the determination of VDN in blood samples and it can be used in routine every day analysis by clinical and forensic laboratories for pharmacokinetic studies, for therapeutic drug level monitoring or for the investigation of related forensic cases. A few blood samples analyzed using the developed method is reported herein to demonstrate the suitability of the method.     

Development and validation of a gas chromatography-mass spectrometric method for the determination of sildenafil and desmethyl-sildenafil in whole blood

Sildenafil (SDL) is a phosphodiesterase type 5 inhibitor and it is approved for the treatment of erectile dysfunction and pulmonary hypertension. SDL is extensively metabolized to its pharmacologically active metabolite, desmethyl‐sildenafil (DSDL). A sensitive and specific GC/MS method for the determination of SDL and DSDL in whole blood was developed and validated to support therapeutic drug monitoring of SDL patients. The combination of solid‐phase extraction with derivatization using BSTFA with 1% TMCS in acetonitrile efficiently reduced matrix effect and improved sensitivity of the method. In this assay, protriptyline was used as internal standard for both analytes. The LODs were 1.50 and 5.00 ng/mL for SDL and DSDL, respectively, whereas the respective LOQs were 5.00 and 15.0 ng/mL. The calibration curves were linear up to 500.0 ng/mL (SDL: R² 0.992, DSDL: R² 0.990). Absolute recovery values for both analytes ranged from 83.1 to 93.2%. Within‐ and between‐batch accuracy was less than 11.8 and 10.2%, respectively, whereas within‐ and between‐batch precision was less than 8.1 and 10.8%, correspondingly. The developed method is suitable for the determination of SDL and DSDL concentrations in blood samples obtained from patients under Viagra^® treatment, for pharmacokinetic studies or for the investigation of related forensic cases.     

Simulations of laser experiments of radiative and non-radiative shocks

The Center for Radiative Shock Hydrodynamics (CRASH) at the University of Michigan was established to study the properties of radiative shocks using both numerical simulation and shock-tube experiments on the Omega Laser at the University of Rochester. The laser accelerates a thin Be disk, which acts like a piston, driving a shock with an initial propagation velocity of 200 km/s into a tube filled with Xe. Analytic estimates indicate that a shock propagating with a velocity greater than about 60 km/s through Xe under these conditions should be strongly radiative. This paper discusses numerical simulations of a proposed modification to this experiment that produces a non-radiative shock. Comparison of the radiative and non-radiative cases provides an excellent opportunity for assessing the effects of radiation on shock structure and flow morphology. For the non-radiative case, the initial shock speed is reduced to 20 km/s by increasing the thickness of the Be disk and by decreasing the energy of the laser. Two-dimensional simulations of targets with cylindrical shock tubes and three-dimensional simulations of more complex targets with elliptical shock tubes are described. In addition, the effect of the shock speed on the cross-sectional area of the tube is discussed.     

A modified protocol for isolation and purity evaluation of a staphylococcal acidic polysaccharide by chromatography and capillary electrophoresis

The extracellular slime of Staphylococcus epidermidis contains, amongst various macromolecules, an acidic polysaccharide (PS) of a molecular mass of 20 kDa with significant antigenic and biological properties. The isolation procedure used so far includes multiple fractionations in anion‐exchange chromatographic columns before its final purification by gel filtration chromatography. This protocol is laborious, time‐consuming and includes the risk of unnecessary loss of PS quantities. Because of the significance of this PS, a modified protocol resulting in an easier and quicker isolation procedure was developed. Furthermore, identification, purity, charge density and molecular integity of the isolated polysaccharide were evaluated by a reverse‐polarity capillary electrophoresis method. Copyright © 2010 John Wiley & Sons, Ltd.     

Interactive System for Similarity-Based Inspection and Assessment of the Well-Being of mHealth Users

Recent digitization technologies empower mHealth users to conveniently record their Ecological Momentary Assessments (EMA) through web applications, smartphones, and wearable devices. These recordings can help clinicians understand how the users’ condition changes, but appropriate learning and visualization mechanisms are required for this purpose. We propose a web-based visual analytics tool, which processes clinical data as well as EMAs that were recorded through a mHealth application. The goals we pursue are (1) to predict the condition of the user in the near and the far future, while also identifying the clinical data that mostly contribute to EMA predictions, (2) to identify users with outlier EMA, and (3) to show to what extent the EMAs of a user are in line with or diverge from those users similar to him/her. We report our findings based on a pilot study on patient empowerment, involving tinnitus patients who recorded EMAs with the mHealth app TinnitusTips. To validate our method, we also derived synthetic data from the same pilot study. Based on this setting, results for different use cases are reported.     

Investigation of the identification point system adaptation in cocaine,benzoylecgonine and ecgonine methyl ester using a single quadrupole mass spectrometer

At present, no official criteria exist for drug identification using single quadrupole mass spectrometers although the European Union (EU) criteria for compound identification have been adopted. These criteria are evaluated with respect to the confirmation of cocaine and its metabolites by single quadrupole liquid chromatography/mass spectrometry (LC/MS) and problems are highlighted. Spiked samples, proficiency testing samples, certified reference materials and samples from real cases that had screened positive for cocaine derivatives by immunoassay were subjected to confirmation by LC/MS using single ion monitoring with in‐source fragmentation. The EU criteria for compound identification were applied for the confirmation of cocaine, benzoylecgonine and ecgonine methyl ester. The use of the identification point (IP) system in spiked, proficiency testing samples and certified reference materials provided acceptable results in all cases while in some cases real positive samples did not provide acceptable results. Failure to meet the EU criteria was attributed to low fragmentation at the lower concentrations and the ion suppression effect while both factors affected compliance with the IP system. The identification of cocaine and its metabolites was considerably improved by using a combination of ammonium formate and formic acid as the LC mobile phase. It appears that poor in‐source fragmentation in single quadrupole LC/MS and ion suppression may constitute a problem with drug identification when implementing the IP system in real samples, resulting in false negative results. Further investigation is needed for the use of such IP systems to be suitable for use in LC/MS methods. Copyright © 2009 John Wiley & Sons, Ltd.