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A novel strategy to trace the origins of commercial pharmaceutical products has been developed based on the direct chemical profiling of the pharmaceutical products by surface desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS). Besides the unambiguous identification of active drug components, various compounds present in the matrixes are simultaneously detected without sample pretreatment, providing valuable information for drug quality control and origin differentiation. Four sources of commercial amoxicillin products made by different manufacturers have been successfully differentiated. This strategy has been extended to secerning six sources of Liuwei Dihuang Teapills, which are herbal medicine preparations with extremely complex matrixes. The photolysis status of chemical drug products and the inferior natural herd medicine products prepared with different processes (e.g., extra heating) were also screened using the method reported here. The limit of detection achieved in the MS/ MS experiments was estimated to be 1 ng/g for amoxicinin inside the capsule product. Our experimental data demonstrate that DAPCI-MS is a useful tool for rapid pharmaceutical analysis, showing promising perspectives for tracking the entire pharmaceutical supply chain to prevent counterfeit intrusions. 10.1021/ac100407k

A homemade novel nanoextractive electrospray ionization (nanoEESI) source has been characterized for in situ mass spectrometric analysis of ambient samples without sample pretreatment. The primary ions generated using a nanospray emitter interact with the neutral sample plume created by manually nebulizing liquid samples, allowing production of the analyte ions in the spatial cross section of the nanoEESI source. The performance of nanoEESI is experimentally investigated by coupling the nanoEESI source to a commercial LTQ mass spectrometer for rapid analysis of various ambient samples using positive/negative ion detection modes. Compounds of interest in actual samples such as aerosol drug preparations, beverages, milk suspensions, farmland water, and groundwater were unambiguously detected using tandem nanoEESI ion trap mass spectrometry. The limit of detection was low picogram per milliliter levels for the compounds tested. Acceptable relative standard deviation (RSD) values (5-10%) were obtained for direct measurement of analytes in complex matrixes, providing linear dynamic signal responses using manual sample introduction. A single sample analysis was completed within 1.2 s. Requiring no sheath gas for either primary ion production or neutral sample introduction, the nanoEESI has advantages including readiness for miniaturization and integration, simple maintenance, easy operation, and low cost. The experimental data demonstrate that the nanoEESI is a promising tool for high-throughput, sensitive, quantitafive, in situ analysis of ambient complex samples, showing potential applications for in situ analysis in multiple disciplines including but not limited to pharmaceutical analysis, food quality control, pesticides residue detection, and homeland security.

Microelectrode voltammetry has been considered to be a powerful technique for single biological cell analysis and brain research. In this paper, we have developed a simple method to get highly sensitive carbon fiber nanoelectrodes (CFNE) modified by single-walled carbon nanotubes (SWNTs) on the basis of our previous work. The electrochemical behavior of SWNTs/CFNE was characterized by potassium ferricyanide, dopamine (DA), epinephrine (E), and norepinephrine (NE) using cyclic voltammetry (CV). Compared with CFNE, SWNTs/CFNE has a much larger available internal surface area per external geometric area, which is supported by SEM images. The modified electrodes show very high sensitivity and favorable electrochemical behavior toward these neurotransmitters. The peak current increases lineary with the concentration of DA, E, and NE in the range of 1.0 x [10.sup.-7] -1.0 x [10.sup.-4], 3.0 x [10.sup.-7] -1.0 x [10.sup.-4], and 5.0 x [10.sup.-7] -1.0 x [10.sup.-4]M, respectively. The CV detection limits (S/N=3) of DA, E, and NE is 7.7 x [10.sup.-9], 3.8 x [10.sup-8] x 4.2 x [10.sup.-8]M, respectively. The modified electrode exhibited almost the same electrochemical behavior after 15 days, indicating that SWNTs/CFNE is pretty stable and has good reproducibility.

Two enzymatic reactions combined with capillary electrophoresis (CE) are used to determine glucose contained in sample volumes of [less than or equal to]500 nL. In the first enzymatic reaction, glucose is oxidized in the presence of glucose oxidase producing hydrogen peroxide, which reacts quantitatively with the fluorogenic compound homovanillic acid catalyzed by the enzyme peroxidase. The second reaction generates a fluorescent species that is proportional to the glucose concentration. The reaction product is determined by CE using laser-induced fluorescence (LIF) as the detection mode. The overall reaction scheme is faster than commonly used precolumn derivatization procedures and can be performed using very small sample quantities. Alternatively, the enzymatic reactions can be performed on-column, similar to the electrophoretically mediated microanalysis approach, accommodating sample quantifies in the nanoliter range. The on-column reaction is a simple and practical approach for the determination of glucose contained in low-volume samples by CE-LIF, where samples are injected directly into the capillary column without any pretreatment. However, sample handling and detectability of the precolumn approach proved to be superior. Determination of glucose using the precolumn and on-column reactions showed detection limits of 50 and 800 nM, respectively. The methods were shown to be linear in the range tested, 1-100 [[micro]Molar] and 100 nM-30 [[micro]Molar], for the on-column and precolumn reactions, respectively. The reproducibility for each scheme was < 5% RSD. To determine the possibility of using a noninvasive procedure for glucose monitoring, we used the CE-LIF methods to analyze human tear samples for glucose. The tear fluid samples were contained in a volume of [approximately]200 nL. The concentration of glucose in the human tear samples analyzed using the precolumn and on-column procedures was [approximately]138 [[micro]Molar].

Four end-functionalized star polymers that could attenuate the flow of ionic currents across biological ion channels were first de novo designed computationally, then synthesized and tested experimentally on mammalian K+ channels. The 4-arm ethylene glycol conjugate star polymers with lysine or a tripeptide attached to the end of each arm were specifically designed to mimic the action of scorpion toxins on K+ channels. Molecular dynamics simulations showed that the lysine side chain of the polymers physically occludes the pore of Kv1.3, a target for immuno-suppression therapy. Two of the compounds tested were potent inhibitors of Kv1.3. The dissociation constants of these two compounds were computed to be 0.1 μM and 0.7 μM, respectively, within 3-fold to the values derived from subsequent experiments. These results demonstrate the power of computational methods in molecular design and the potential of star polymers as a new infinitely modifiable platform for ion channel drug discovery. [ABSTRACT FROM AUTHOR]

Pentachlorophenol (PCP) has been used extensively as a biocide and a wood preservative and has been reported to be immunosuppressive in rodents and humans. Tetrachlorohydroquinone (TCHQ) is a major metabolite of PCP. TCHQ has been identified as the main cause of PCP-induced genotoxicity due to reactive oxidant stress (ROS). However, the precise mechanisms associated with the immunotoxic effects of PCP and TCHQ remain unclear. The aim of this study was to examine the effects of PCP and TCHQ on the induction of ROS and injury to primary mouse splenocytes. Our results shown that TCHQ was more toxic than PCP and that a high dose of TCHQ led to necrotic cell death of the splenocytes through induction of massive and sudden ROS and prolonged ROS-triggered ERK activation. Inhibition of ROS production by N-acetyl-cysteine (NAC) partially restored the mitochondrial membrane potential, inhibited ERK activity, elevated caspase-3 activity and PARP cleavage, and, eventually, switched the TCHQ-induced necrosis to apoptosis. We suggest that prolonged ERK activation is essential for TCHQ-induced necrosis, and that ROS play a pivotal role in the different TCHQ-induced cell death mechanisms. [ABSTRACT FROM AUTHOR]

Both acetonyltriphenylphosphonium bromide (ATPB) and poly-p-styryldiphenylacetonylphosphonium bromide (PATPB) are excellent catalysts in the protection of aldehydes as acetals or thioacetals. In general, ATPB is highly selective as ketones do not give good yields of ketals with this catalyst. [ABSTRACT FROM AUTHOR]

Titanomagnetite is widely distributed in nature, and has potentials in environmental remediation. Nanometric titanomagnetite particles were usually prepared via soft chemistry routes in aqueous solutions. Herein a novel soft chemistry route carried out in a deep eutectic solvent (DES) comprising choline chloride and urea in a molar ratio of 1:2 was successfully developed to make titanomagnetite nanoparticles (Fe 2.5 Ti 0.5 O 4 -DES, ~30 nm). The chemical composition analyzed by different methods revealed that Fe 2.5 Ti 0.5 O 4 -DES nanoparticles possess the Ti-rich core and Fe-rich shell. The Fe 2.5 Ti 0.5 O 4 -DES nanoparticles exhibited enhanced activities in catalytic decomposition of H 2 O 2 and oxidative degradation of organic contaminants at circumneutral pH values and room temperature, which was mainly attributed to the increased content of ferrous (Fe2+) ions upon substitution of Ti4+ for ferric (Fe3+) ions in spinel structure of magnetite. Unlabelled Image • Synthesis of titanomagnetite magnetic nanoparticles (TMMNPs) in deep eutectic solvent • TMMNPs have Ti-rich core and Fe-rich shell. • TMMNPs exhibited enhanced catalytic activity due to increased Fe2+ content. [ABSTRACT FROM AUTHOR]