Automated on-line in-tube solid-phase microextraction coupled with HPLC/MS/MS for the determination of butyrophenone derivatives in human plasma

This paper describes a fully automated on-line method combining in-tube solid-phase microextraction (SPME) in which sample clean-up and enrichment are conducted through an open tubular fused-silica capillary column and high-performance liquid chromatography (HPLC)/tandem mass spectrometry (MS/MS) detection for the determination of six butyrophenone derivatives (moperone, floropipamide, haloperidol, spiroperidol, bromperidol, and pimozide) in human plasma samples. The six butyrophenones were extracted by repeatedly aspirating and dispensing plasma sample solutions on a DB-17 capillary column (60 cm × 0.32 mm i.d., film thickness 0.25 μm). The analytes retained on the inner surface of the capillary column were then eluted into an acetonitrile-rich mobile phase using a gradient separation technique. Extraction efficiencies ranged from 12.7% to 31.8% for moperone, spiroperidol, and pimozide, and from 1.08% to 4.86% for floropipamide, haloperidol, and bromperidol. The regression equations for all compounds showed excellent linearity, ranging from 0.05 to 50 ng/0.1 mL of plasma, except for moperone and spiroperidol (0.01 to 50 ng/0.1 mL). The limits of detection and quantification in plasma for each drug were 0.03–0.2 and 0.1–0.5 ng/mL, respectively. The intra- and inter-day coefficients of variation for all compounds in plasma were not greater than 13.7%.     

Stereoselective reduction of β hydroxyketones to 1,3-diols highly selective 1,3-asymmetric induction via boron chelates

Highly selective asymmetric induction can be achieved in the reduction of acyclic β-hydroxyketones via boron chelates. Treatment of β-hydroxyketones (1) with tributyl or tri-isobutylborane and successively with sodium borohydride afforded syn-1,3-diols (3) in highly stereo-selective manner, Syn -α-substituted-β -hydroxyketones (8) were also reduced to give syn, syn-1,3-diols (9) exclusively. The reaction was further applied to the convenient preparation of 3-deoxy-hexoses.     

One-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinones and terminal acetylenes

In this paper, a concise one-pot method for the construction of benzo[f]indole-4,9-dione motifs is described. These transformations proceed via a sequential palladium- and copper-catalyzed coupling reaction of 1,4-naphthoquinones with terminal acetylenes, followed by a copper-catalyzed intramolecular cyclization reaction of the resulting coupling product.     

Buffers to suppress sodium dodecyl sulfate adsorption to polyethylene oxide for protein separation on capillary polymer electrophoresis

Although polyethylene oxide (PEO) offers several advantages as a sieving polymer in SDS capillary polymer electrophoresis (SDS-CPE), solution properties of PEO cause deterioration in the electrophoresis because PEO in solution aggregates itself, degrades into smaller pieces, and forms polymer-micelle complexes with SDS. We examined protein separation on SDS-CPE with PEO as a sieving matrix in four individual buffer solutions: Tris-CHES, Tris-Gly, Tris-Tricine, and Tris-HCl buffers. The solution properties of PEO as a sieving matrix in those buffers were examined by dynamic light scattering (DLS) and by surface tension. Preferential SDS adsorption onto PEO disturbed protein-SDS complexation and impaired the protein separation efficiency. Substantial adsorption of SDS to PEO was particularly observed in Tris-Gly buffer. The Tris-CHES buffer prevented SDS from adsorbing onto the PEO. Only Tris-CHES buffer achieved separation of six proteins. This study demonstrated efficient protein separation on SDS-CPE with PEO.     

Direct Visualization of Electromagnetic Microfields by Superposition of Two Kinds of Electron Holograms

A new electron holographic method is presented to directly visualize pure phase objects such as electromagnetic microfields, which is achieved by superposition of two kinds of electron holograms. The method is very simple and is twice as sensitive as the conventional double-exposure electron holography and the four-electron-wave interference. Using this technique, an electric field around a charged latex sphere and a magnetic field around a barium ferrite particle have been directly observed.     

Indium-mediated beta-allylation,beta-propargylation,and beta-allenylation onto alpha,beta-unsaturated ketones: reactions of in-situ-generated 3-tert-butyldimethylsilyloxyalk-2-enylsulfonium salts with in-situ-generated organoindium reagents

3-tert-Butyldimethylsilyloxyalk-2-enylsulfonium salts, generated in situ from the reaction of alpha,beta-enones with dimethyl sulfide in the presence of TBSOTf, underwent a novel nucleophilic substitution with allylindiums to give silyl enol ethers of delta,epsilon-alkenyl ketones in good yields, which correspond to formal Michael addition products. In a similar manner, 1,4-propargylation of propargylindiums onto the sulfonium salts produced the corresponding silyl enol ethers of delta,epsilon-alkynyl ketones in good yields. Organoindium reagents derived from gamma-substituted propargyl bromide and indium afforded the corresponding silyl enol ethers of beta-allenyl ketones in good yields. The reaction proceeds via an addition-substitution mechanism involving the formation of allylic sulfonium salts. The presence of the intermediate sulfonium salt was confirmed by observation of the low-temperature (1)H NMR spectra.     

Robust and simple interface for microchip electrophoresis-mass spectrometry

A robust and simple interface for microchip electrophoresis-mass spectrometry (MCE-MS) was developed using a spray nozzle connected to the exit of the separation channel of the microchip. The spray nozzle was attached to the microchip using a polyether ether ketone screw without adhesive, thus allowing easy replaced. Sample injection and electrophoretic separation was performed by control of the voltage only. The analysis of a few basic drugs was performed using the optimized MCE-MS system. The separation was improved by using a high-viscosity separation buffer and a spray nozzle with a small bore size. This system was also applied to the separation of peptides and protein-trypsin digests. Sample adsorption was minimized by adding acetonitrile to the separation buffer when using a quartz microchip.     

Collision-energy-resolved Penning ionization electron spectroscopy of p-benzoquinone: study of electronic structure and anisotropic interaction with He(*)(2 (3)S) metastable atoms

Collision energy dependence of partial ionization cross sections (CEDPICS) of p-benzoquinone with He(*)(2 (3)S) metastable atoms indicates that interaction potentials between p-benzoquinone and He(*)(2 (3)S) are highly anisotropic in the studied collision energy range (100-250 meV). Attractive interactions were found around the C==O groups for in-plane and out-of-plane directions, while repulsive interactions were found around CH bonds and the benzenoid ring. Assignment of the first four ionic states of p-benzoquinone and an analogous methyl-substituted compound was examined with CEDPICS and anisotropic distributions of the corresponding two nonbonding oxygen orbitals (n(O) (+),n(O) (-)) and two pi(CC) orbitals (pi(CC) (+),pi(CC) (-)). An extra band that shows negative CEDPICS was observed at ca. 7.2 eV in Penning ionization electron spectrum.     

Rapid sequencing and disulfide mapping of peptides containing disulfide bonds by using 1,5-diaminonaphthalene as a reductive matrix

MS/MS is indispensable for the amino acid sequencing of peptides. However, its use is limited for peptides containing disulfide bonds. We have applied the reducing properties of 1,5-diaminonaphthalene (1,5-DAN) as a MALDI matrix to amino acid sequencing and disulfide bond mapping of human urotensin II possessing one disulfide bond, and human guanylin possessing two disulfide bonds. 1,5-DAN was used in the same manner as the usual MALDI matrices without any pre-treatment of the peptide, and MS/MS was performed using a matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometer (MALDI QIT TOFMS). The results demonstrated that MS/MS of the molecular ions reduced by 1,5-DAN provided a series of significant b-/y-product ions. All 11 amino acid residues of urotensin II were identified using 1,5-DAN, while only 5 out of 11 residues were identified using 2,5-dihydroxybenzoic acid (DHB); similarly 11 out of 15 amino acid residues of guanylin were identified using 1,5-DAN, while only three were identified using DHB. In addition, comparison of the theoretical and measured values of the mass differences between corresponding MS/MS product ions using 1,5-DAN and DHB narrowed down the possible disulfide bond arrangement candidates. Consequently, 1,5-DAN as a reductive matrix facilitates rapid amino acid sequencing and disulfide mapping for peptides containing disulfide bonds.