Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of nobiletin in rat plasma: application to a pharmacokinetic study

A highly sensitive, rapid assay method has been developed and validated for the estimation of nobiletin in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The assay procedure involves extraction of nobiletin and citalopram (internal standard, IS) from rat plasma with liquid–liquid extraction. Chromatographic separation wa s achieved using an isocratic mobile phase (0.2% formic acid–acetonitrile, 20:80, v/v) at a flow rate of 0.6 mL/min on an Atlantis dC₁₈ column (maintained at 40 ± 1 °C) with a total run time of 2.0 min. The MS/MS ion transitions monitored were 403.2 → 373.0 for nobiletin and 325.2 → 109.0 for IS. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.05 ng/mL and the linearity range extended from 0.05 to 51.98 ng/mL. The intra‐ and inter‐day precisions were in the range of 1.96–14.3 and 6.21–12.1, respectively. Copyright © 2012 John Wiley & Sons, Ltd.     

Development and validation of a highly sensitive method for the determination of abiraterone in rat and human plasma by LC-MS/MS-ESI: application to a pharmacokinetic study

A highly sensitive, rapid assay method has been developed and validated for the estimation of abiraterone (ART) in rat and human plasma with liquid chromatography coupled to tandem mass spectrometry and electrospray ionization in the positive-ion mode. The assay procedure involves extraction of ART and phenacetin (internal standard, IS) from rat and human plasma with a simple protein precipitation extraction process. Chromatographic separation was achieved using an isocratic mobile (10 mm ammonium acetate:acetonitrile, 10:90, v/v) at a flow-rate of 0.70 mL/min on an Atlantis dC(18) column maintained at 40 °C with a total run time of 3.5 min. The MS/MS ion transitions monitored were 350.3 → 156.0 for ART and 180.2 → 110.1 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.20 ng/mL and the linearity range extended from 0.20 to 201 ng/mL. The intra- and inter-day precisions were in the ranges 2.39-10.4 and 4.84-9.53% in rat plasma and 3.82-10.8 and 6.97-8.94% in human plasma.     

Synthesis of functional hybrid silica scaffolds with controllable hierarchical porosity by dynamic templating

We report a facile one-pot synthesis of hierarchically porous scaffolds, with independent control over nanoparticle mesoporosity and scaffold macroporosity. Our technique combines the chemistry of mesoporous silica nanoparticles with the control afforded by dynamic templating of surfactant mesophases. These materials are readily functionalizable and allow controllable spatial variation in macroporosity.     

Presence detection under optimum fusion in an ultrasonic sensor system

Reliable presence detection is a requirement in energy-efficient occupancy-adaptive indoor lighting systems. A system of multiple ultrasonic sensors is considered for presence detection, and the performance gain from optimum fusion is studied. Two cases are considered wherein an individual sensor determines presence based on (i) local detection by processing echoes at its receiver, and (ii) the optimum Chair-Varshney fusion rule using multiple sensor detection results. The performance gains of using optimum fusion over local detection are characterized under different sensor system configurations and it is shown that improved detection sensitivity is obtained over a larger detection coverage region.     

Speech enhancement using a generic noise codebook

Although single-microphone noise reduction methods perform well in stationary noise environments, their performance in non-stationary conditions remains unsatisfactory. Use of prior knowledge about speech and noise power spectral densities in the form of trained codebooks has been previously shown to address this limitation. While it is possible to use trained speech codebooks in a practical system, the variety of noise types encountered in practice makes the use of trained noise codebooks less practical. This letter presents a method that uses a generic noise codebook for speech enhancement that can be generated on-the-fly and provides good performance.     

Do current-density nonlinearities cut off the glass transition?

Extended mode-coupling theories for dense fluids predict that nonlinear current-density couplings cut off the singular "ideal glass transition" present in the standard mode-coupling theory where such couplings are ignored. We suggest here that, rather than allowing for activated processes as sometimes supposed, contributions from current-density couplings are always negligible close to a glass transition. We discuss in schematic terms how activated processes can nonetheless cut off the transition by causing the memory function to become linear in correlators at late times.     

Highly Diastereoselective Total Syntheses of (+)‐7‐Epigoniodiol, (−)‐8‐Epigoniodiol,and (+)‐9‐Deoxygoniopypyrone

An expedient concise total synthesis of (+)‐7‐epigoniodiol, (?)‐8‐epigoniodiol, and (+)‐9‐deoxygoniopypyrone is accomplished. The key transformations include a catalytic hydroxylation and base‐mediated N‐(acetyl)oxazolidinone addition reactions, which could set the consecutive OH motif that is either syn,syn or syn,anti with high diastereoselectivity. Moreover, this approach envisioned to facilitate the synthesis of other representatives of the family with structural and stereochemical variation.     

Some Tetrahedral Coordination Polymers of Zinc(II), Cadmium(II), and Mercury(II) Involving 4-Aminomethylpyridine

Abstract

Analytical data and infrared spectral measurements down to 200 cm^?1 on the 1:1 compounds formed by the interaction of zinc(II) and cadmium(II) thiocyanates and mercury(II) chloride and bromide with 4-aminomethylpyridine indicate that the compounds are coordination polymers having tetrahedral stereochemistry with bidentate bridging 4-aminomethylpyridine molecules and terminally bonded halogen/pseudohalogen groups in the solid state.     

Bioinspired Nitroalkylation for Selective Protein Modification and Peptide Stapling

Nitroalkanes react specifically with aldehydes, providing rapid, stable, and chemoselective protein bioconjugation. These nitroalkylated proteins mimic key post‐translational modifications (PTMs) of proteins and can be used to understand the role of these PTMs in cellular processes. Demonstrated here is the substrate scope of this bioconjugation by attaching a variety of tags, such as NMR tags, fluorescent tags, affinity tags, and alkyne tags, to proteins. The structure and enzymatic activity of modified proteins remain conserved after labeling. Notably, the nitroalkane group leads to easy characterization of proteins by mass spectrometry because of its distinct fingerprint pattern. Importantly, the nitro‐alkylated peptides provide a new handle for site‐selective fluorination of peptides, thus installing a specific probe to study peptide–protein interactions by ¹⁹F NMR spectroscopy. Furthermore, nitroalkane reagents can be used for the late‐stage diversification of peptides and for the synthesis of peptide staples.