Simultaneous determination of benzimidazoles and their metabolites in plasma using high-performance liquid chromatography/tandem mass spectrometry: application to pharmacokinetic studies in rabbits

An HPLC/MS/MS method was developed for the simultaneous determination of the following benzimidazole anthelmintics and metabolites in plasma: flubendazole, albendazole, fenbendazole, mebendazole, thiabendazole, hydrolyzed flubendazole, albendazole sulfoxide, albendazole sulfone, albendazole aminosulfone, oxfendazole, fenbendazole sulfone, aminomebendazole, hydroxymebendazole, and 5-hydroxythiabendazole. The sample preparation process involved a pH-dependent extraction of the analytes. Chromatographic separation was performed on a C18 column with a mobile phase gradient starting with methanol-water (20 + 80, v/v) containing 0.1% formic acid. The overall average recoveries of the analytes based on a matrix-matched calibration ranged from 75.0 to 120.0%, with RSD values of <20.0%. The LODs ranged from 0.08 to 2.0 microg/kg and the LOQs from 0.3 to 5.0 microg/kg. The validated method was used in pharmacokinetic studies of benzimidazole compounds in rabbits, and the elimination of the metabolites was measured quantitatively.     

Emission control by binary energy transfer processes on oligouridine

Fluorescent oligonucleotides have been designed on which two different energy transfer processes were mounted together: excitonic interaction and FRET. The fluorescence emission of the oligonucleotides was controlled well by the two different energy transfer processes, in response to their hybridization to the complementary RNA both in vitro and in cells.     

A novel prenylated xanthone from the stems and leaves of Calophyllum inophyllum

A novel prenylated xanthone, caloxanthone Q, was isolated from the stems and leaves of Calophyllum inophyllum. The structure elucidation was carried out by detailed spectroscopic analysis.     

Magnetic solid-phase extraction using magnetic hypercrosslinked polymer for rapid determination of illegal drugs in urine

A novel magnetic material Fe₃O₄/SiO₂/P(MAA‐co‐VBC‐co‐DVB) was prepared via the hypercrosslinking of its precursor which was produced via precipitation polymerization of methacrylic acid (MAA), vinylbenzyl chloride (VBC), and divinylbenzene (DVB) in the presence of Fe₃O₄/SiO₂ submicrospheres with the surface containing abundant reactive double bonds. The resultant sorbent was characterized by scan electron microscopy, N₂ adsorption, and Fourier transform infrared spectroscopy. It was found that this material had remarkable features such as large surface area (500 m²/g) and pore volume (0.32 cm³/g), as well as desirable chemical composition (including hydrophobic and ion‐exchange moieties). Taking advantages of the Fe₃O₄/SiO₂/P(MAA‐co‐VBC‐co‐DVB), a magnetic SPE (MSPE) coupled with capillary electrophoresis (CE) method was developed for the determination of illegal drugs in urine samples. The extraction time could be clearly shortened up to 3 min. The recoveries of these drug compounds were in the range of 84.0–123% with relative standard deviations ranging between 1.7 and 10.5%; the limit of detection was in the range of 4.0–6.0 μg/L. The proposed method is simple, effective, and low‐cost, and provides an accurate and sensitive detection platform for abused drug analysis.     

Synthesis and antitumoral activity of gelatin/polyoxometalate hybrid nanoparticles

Surfactant-free gelatin/heptamolybdate (HM) hybrid nanoparticles are prepared by a simple and environmentally friendly approach utilizing the electrostatic interaction between anionic HM and the zwitterionic gelatin. The obtained nanoparticles have a tunable size and very high HM loading content up to about 70%. In vitro and in vivo experiments prove that the gelatin/HM hybrid nanoparticles exhibit significantly better antitumor activity than plain ammonium heptamolybdate solution. Therefore, the gelatin/HM hybrid nanoparticles reported here may serve as a prototype platform for polymer/polyoxometalate (POM) hybrid nanoparticles as cancer treatment agents and hence open up more opportunities to maximize the potential of POM-based pharmaceutical agents.     

Analysis of doxorubicin uptake in single human leukemia K562 cells using capillary electrophoresis coupled with laser-induced fluorescence detection

The doxorubicin (DOX) uptake in single human leukemia K562 cells with changes in both drug dosage and exposure period was studied using capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF) detection. The cells were treated with DOX at different concentrations (1, 3, 10, 20, 30, and 50 μM) and for different exposure times (1, 3, 5, 24, and 48 h). At least 20 cells were analyzed for each DOX-treated cell population. A marked heterogeneity in DOX uptake among single cells was observed, because the relative standard deviation of the uptake of DOX by single cells ranged from 24.0% to 61.1% within each cell population. The cell-to-cell heterogeneity in DOX uptake first decreased and then became constant with increasing drug concentration, but it did not exhibit regular variation with increasing exposure time. The mean DOX uptake was a linear function of drug concentration (r ≥ 0.9667). In terms of the correlation with exposure time, the mean DOX uptake reached its maximum at 3 h for the cell populations treated with 1–10 μM DOX, while it kept increasing during 48 h exposure of cell populations to 20–50 μM DOX. Because it eliminates DOX fluorescence quenching and sample loss, the CE-LIF method directly detects the true DOX uptake by single cells, and thus presents accurate information on both the cell-to-cell heterogeneity in DOX uptake and the patterns of DOX uptake in K562 cells as functions of drug concentration and exposure time.     

Highly specific capture and direct MALDI-MS analysis of phosphorylated peptides using novel multifunctional chitosan-GMA-IDA-Fe (III) nanosphere

In this study, we describe a method for highly specific enrichment of phosphopeptides with multifunctional chitosan–glycidyl methacrylate (GMA)–iminodiacetic acid (IDA)–Fe (III) nanospheres for direct analysis by matrix-assisted laser desorption–ionization mass spectrometry (MALDI-MS). This is the first time that chitosan has been used to create nanospheres support material for selective enrichment of phosphopeptides by modification with GMA, derivatization with IDA, and loading with Fe (III) ions. Chitosan-GMA-IDA-Fe (III) nanospheres with a diameter of 20 to 100 nm have multifunctional chemical moieties which confer unique properties, good dispersibility in highly acidic binding buffers, as well as good biocompatibility and chemical stability which improves their specific interaction with phosphopeptides using various types of acid binding buffers. The process of enrichment is very simple, quick, efficient, and specific. Its high specificity and efficiency for purification of phosphopeptides is reflected in the very low and substoichiometric amounts of phosphopeptides which can be detected, in quantities as low as 1:3,000 M ratios. Compared with other state-of the-art technologies such as the use of conventional Fe³⁺-IMAC and TiO₂, these chitosan nanosphere techniques show superior specificity and sensitivity. Moreover, the resultant chitosan-GMA-IDA-Fe³⁺ nanosphere-absorbed phosphopeptides can be either directly analyzed by MALDI-TOF MS analysis or eluted and further analyzed by nano-LC-MS/MS.     

A note on the Jacobian Conjecture

In this note, we show that, if the Druzkowski mappings F(X)=X+(AX)^∗3, i.e. F(X)=(x₁+(a₁₁x₁+?+a_1nx_n)³,…,x_n+(a_n1x₁+?+a_nnx_n)³), satisfies TrJ((AX)^∗3)=0, then where δ is the number of diagonal elements of A which are equal to zero. Furthermore, we show the Jacobian Conjecture is true for the Druzkowski mappings in dimension ?9 in the case .     

非紧集上不连续函数的Ky Fan不等式及其等价形式和应用

证明了非紧集上不具有任何连续性的函数弱Ky Fan点的存在性,给出了在函数只具非常弱的连续性和凸性条件下非紧集上Ky Fan不等式解的存在性,并给出它的两种等价形式.作为应用:(1)得到Ky Fan截口定理和Fan-Browder不动点定理的推广;(2)应用于博弈理论,得到几个新的Nash平衡存在性定理.     

一类非平稳高斯序列超过数点过程与和的渐近性

设{X_i}_(i=1)~∞是标准化非平稳高斯序列,N_n为X_1,X_2,…,X_n依次对水平μ_(n1),μ_(n2),…,μ_(nn)的超过数形成的点过程.记Υ_(ij)=X_iX_j,S_n=■X_i.当Υ_(ij)满足一定条件时,证明了N_n依分布收敛到Poisson过程,且N_n与S_n渐近独立.