Identification and structural characterization of in vivo metabolites of ketorolac using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS)

In vivo metabolites of ketorolac (KTC) have been identified and characterized by using liquid chromatography positive ion electrospray ionization high resolution tandem mass spectrometry (LC/ESI-HR-MS/MS) in combination with online hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, blood urine and feces samples were collected after oral administration of KTC to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation and freeze liquid separation followed by solid-phase extraction and then subjected to LC/HR-MS/MS analysis. A total of 12 metabolites have been identified in urine samples including hydroxy and glucuronide metabolites, which are also observed in plasma samples. In feces, only O-sulfate metabolite and unchanged KTC are observed. The structures of metabolites were elucidated using LC-MS/MS and MS(n) experiments combined with accurate mass measurements. Online HDX experiments have been used to support the structural characterization of drug metabolites. The main phase I metabolites of KTC are hydroxylated and decarbonylated metabolites, which undergo subsequent phase II glucuronidation pathways.     

青蒿素与氯化血红素作用的荧光研究及分析应用

介绍了吡罗红为指示剂通过荧光降低法研究青蒿素与氯化血红素之间的相互作用。实验发现两者为酶和底物作用模型,作用位点为药物的过氧基团和氯化血红素活性中心的金属离子,其动力学催化常数K_m, V_max和K_cat分别为8.4×10-5 mol·L-1, 7.4×10-6 mol·L-1·s-1及50.23 s-1,催化活性分别受去激活剂和高温影响。在最佳条件下, 荧光降低值ΔF(F₀-F)与青蒿素浓度在0.0～1.27×10-6 mol·L-1范围内成线性关系, 检测限为2.3×10-8 mol·L-1, 该方法已用于测定血浆和尿液介质中的微量青蒿素。     

磁边界效应对径向磁场中等离子体束流运动轨迹的影响

根据离子与径向磁场的约束关系，用面向对象的单元粒子法模拟了极向偏转器中等离子体束流在均匀和非均匀径向磁场中的运动情况，得到了在磁边界效应下极向偏转器内部畸变电场的分布，分析了对质量分离的影响。模拟成果对质量分离器、质谱分析仪及材料提纯等装置的研制、特殊位形电磁场控制多质量束流等相关领域的研究有参考价值。     

光谱法及分子模拟研究青蒿素与小牛胸腺DNA的相互作用

在pH 7.4的Tris-HCl缓冲溶液中,采用紫外吸收光谱、荧光光谱结合溴化乙锭（EB）荧光探针、共振散射光谱以及DNA熔点（T_m）实验和分子模拟等技术,研究了青蒿素（QHS）与小牛胸腺DNA（ctDNA）分子间结合位点与结合机制。光谱实验结果显示,QHS与DNA发生减色效应,QHS的加入使EB-DNA体系发生静态荧光猝灭,QHS与DNA作用后其467 nm处共振散射峰锐增,与QHS作用引起DNA的T_m值升高5℃,说明QHS竞争性地嵌插入DNA的碱基对中。通过计算获得QHS与DNA间结合常数K_a为1.43×10³ L/mol（298 K）、0.99×10³ L/mol（304 K）。分子模拟结果表明,QHS吡喃环部分结构嵌插到DNA小沟区域GA碱基对间,氢键和范德华力是两者间结合的主要非共价作用方式,该结论与光谱法和热力学所得结果一致。     

Novel approaches for low cost fabrication of SOI

Two trials for low cost manufacture of silicon-on-insulator (SOI) wafers were implemented. Low dose separation by implantation of oxygen (SIMOX) procedure has been conducted on a beam-line ion implanter with mass analyzer. The energy dependence of the formed SOI structure was studied at varied implant dosages. The integrity of the buried oxide (BOX) layer was examined by transmission electron microscopy (TEM) and the threading dislocation in the top silicon layer was evaluated by Secco technique. The results indicated that not only the implanted oxygen dose but also the oxygen ion energy plays an important role in the formation of SOI structure with good crystallinity of top silicon, sharp Si/SiO₂ interfaces and highly integrated BOX layer free of silicon inclusion. For separation by plasma implantation of oxygen (SPIMOX) approach, water plasma, rather than oxygen plasma, was employed to avoid oxygen spread in the implant depth profile. The SPIMOX process using water plasma was carried out on a beam-line ion implanter without mass selector to simulate the plasma implantation procedure. Cross-sectional TEM study revealed that uniform BOX layer was formed under single crystal silicon superficial layer with the present approach. The interfaces between silicon superficial layer, BOX layer and bulk silicon were smooth and sharp. An implant dose window has been identified for fabricating the desirable SOI structure.     

Spin-polarized to valley-polarized transition in graphene bilayers at ν=0 in high magnetic fields

We investigate the transverse electric field (E) dependence of the ν=0 quantum Hall state (QHS) in dual-gated graphene bilayers in high magnetic fields. The longitudinal resistivity ρ(xx) measured at ν=0 shows an insulating behavior which is strongest in the vicinity of E=0, as well as at large E fields. At a fixed perpendicular magnetic field (B), the ν=0 QHS undergoes a transition as a function of the applied E, marked by a minimum, temperature-independent ρ(xx). This observation is explained by a transition from a spin-polarized ν=0 QHS at small E fields to a valley- (layer-)polarized ν=0 QHS at large E fields. The E field value at which the transition occurs follows a linear dependence on B.     

Application of high-resolution ESI and MALDI mass spectrometry to metabolite profiling of small interfering RNA duplex

We investigated the application of a high-resolution Orbitrap mass spectrometer equipped with an electrospray ionization (ESI) source and a matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometer to the metabolite profiling of a model small interfering RNA (siRNA) duplex TSR#34 and compared their functions and capabilities. TSR#34 duplex was incubated in human serum in vitro, and the duplex and its metabolites were then purified by ion exchange chromatography in order to remove the biological matrices. The fraction containing the siRNA duplex and its metabolites was collected and desalted and then subjected to high-performance liquid chromatography (HPLC) equipped with a reversed phase column. The siRNA and its metabolites were separated into single strands by elevated chromatographic temperature and analyzed using the ESI-Orbitrap or the MALDI-TOF mass spectrometer. Using this method, the 5' and/or 3' truncated metabolites of each strand were detected in the human serum samples. The ESI-Orbitrap mass spectrometer enabled differentiation between two possible RNA-based sequences, a monoisotopic molecular mass difference which was less than 2 Da, with an intrinsic mass resolving power. In-source decay (ISD) analysis using a MALDI-TOF mass spectrometer allowed the sequencing of the RNA metabolite with characteristic fragment ions, using 2,4-dihydroxyacetophenone (2,4-DHAP) as a matrix. The ESI-Orbitrap mass spectrometer provided the highest mass accuracy and the benefit of on-line coupling with HPLC for metabolite profiling. Meanwhile, the MALDI-TOF mass spectrometer, in combination with 2,4-DHAP, has the potential for the sequencing of RNA by ISD analysis. The combined use of these methods will be beneficial to characterize the metabolites of therapeutic siRNA compounds. Copyright ? 2012 John Wiley & Sons, Ltd.     

Plasma isotope separation methods

Six major types of isotope separation methods which involve plasma phenomena are discussed. These methods are: plasma centrifuge, AVLIS (atomic vapor laser isotope separation), ion wave, ICR (ion cyclotron resonance), calutron, and gas discharge. The plasma phenomena in these major categories are described. An attempt is made to include enough references so that a more detailed study or evaluation of a particular method could readily be pursued. A brief discussion of isotope separation using mass balance concepts is also included     

Analysis of sonolytic degradation products of azo dye Orange G using liquid chromatography-diode array detection-mass spectrometry

In this paper, seven new sonolytic degradation products of Orange G were found and identified using powerful analytical techniques such as liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS), tandem mass spectrometry (MS/MS), and liquid chromatography with diode-array detection (LC-DAD). Each technique provided complementary information for the degradation products identification. In order to resolve the MS and MS/MS spectra obtained, the separation conditions were optimized. Among them, Orange G was unambiguously identified based on its abundant [M-H](-) ion, [M+H](+) ion, ultra-violet and visible spectra, retention time, and tandem mass spectrometric analysis compared with an authentic standard. The seven new degradation products were tentatively identified based on ultra-violet and visible spectra, [M-H](-) ions, and tandem mass spectrometry. The neutral losses of SO(2), SO(3), N(2) and H(2)O for MS/MS spectra which appear to be characteristic of the negative ion mode were observed. Based on this by-product identification, a possible multi-step degradation scheme is proposed. The analysis results of degradation products reveal that the degradation mechanism proceeds via reductive cleavage of the azo linkage, as well as intermolecular dehydration and desulfonation due to the powerful oxidizing hydroxyl radicals as well as hydrogen radical.     

First observation of the sigma(*+)(c) baryon and a new measurement of the sigma(*+)(c) mass

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.     

Ion separation due to magnetic field penetration into a multispecies plasma

The magnetic field, the electron density, and the ion velocities in a multispecies plasma conducting a high fast-rising current are determined using simultaneous spectroscopic measurements. It is found that ion separation occurs in which a light-ion plasma is pushed ahead while a heavy-ion plasma lags behind the magnetic piston. We show that most of the momentum imparted by the magnetic field pressure is taken by the reflected light ions, and most of the dissipated magnetic field energy is converted into kinetic energy of these ions, even though their mass is only a small part of the total plasma mass. Such species separation with implications to the momenta and energy partitioning is shown to be of a general nature.     

Plasma-optical mass separation of isotopes in the magnetic field of linear current

The existing methods of electromagnetic mass separation are analyzed. The trajectories of ions injected into the separation region along various directions in the magnetic field of a linear current are calculated. On the basis of analysis, two new schemes of mass separators with a plasma accelerator as the ion source are proposed. In the first scheme, plasma is injected along the longitudinal axis of the accelerator, while in the second scheme, an accelerator with annular ejection of the plasma flow along the radius in the direction of the longitudinal axis of the separator is used.     

Experimental demonstration of improved neoclassical transport with quasihelical symmetry

Differences in the electron particle and thermal transport are reported between plasmas produced in a quasihelically symmetric (QHS) magnetic field and a configuration with the symmetry broken. The thermal diffusivity is reduced in the QHS configuration, resulting in higher electron temperatures than in the nonsymmetric configuration for a fixed power input. The density profile in QHS plasmas is centrally peaked, and in the nonsymmetric configuration the core density profile is hollow. The hollow profile is due to neoclassical thermodiffusion, which is reduced in the QHS configuration.     

基于UHPLC-QE-MS的CCI模型大鼠的血清代谢组学研究

采用超高效液相色谱-四级杆静电场轨道阱质谱（UHPLC-QE-MS）非靶向代谢组学方法,观察CCI模型大鼠血清内源性代谢物的变化,筛选出慢性坐骨神经痛大鼠血清差异性代谢物,分析慢性疼痛对差异性代谢物的影响。将12只SPF级SD雄性大鼠随机均分为正常组和坐骨神经慢性压迫损伤（CCI）组,每组6只。CCI组建立大鼠左侧坐骨神经慢性压迫损伤模型,正常组除不结扎坐骨神经,其余步骤一样。14天后腹主动脉采血, 分离血清,对大鼠血清中的代谢物进行代谢组学检测。利用UHPLC-QE-MS技术并结合PCA(主成分分析)筛选差异代谢物,利用MetabolicAnalyst5.0进行差异代谢物的富集分析。富集分析结果表明,与正常对照组相比,CCI模型大鼠血清有机酸、有机杂环化合物、脂肪酰基、碳水化合物、核酸、有机氮化合物、碳氢化合物等9类代谢物具有统计学差异。结果表明：基于UHPLC-QE-MS的血清代谢组学方法能够有效区分正常组和CCI组,筛选出的差异代谢物有助于慢性疼痛的机制及药物靶点研究。     

Evidence of New States Decaying into Xi(*)(c)pi

Using 13.7 fb(-1) of data recorded by the CLEO detector at Cornell Electron Storage Ring, we report evidence of two new charmed baryons: one decaying into Xi(0')(c)pi(+) with the subsequent decay Xi(0')(c)-->Xi(0)(c)gamma, and its isospin partner decaying into Xi(+')(c)pi(-) followed by Xi(+')(c)-->Xi(+)(c)gamma. We measure the following mass differences for the two states: M(Xi(0)(c)gammapi(+))-M(Xi(0)(c)) = 318.2+/-1.3+/-2.9 MeV and M(Xi(+)(c)gammapi(-))-M(Xi(+)(c)) = 324.0+/-1.3+/-3.0 MeV. We interpret these new states as the J(P) = 1 / 2(-) Xi(c1) particles, the charmed-strange analogs of the Lambda(+)(c1)(2593).     

Analysis of cyclic boronated and trimethylsilylated phenolalkylamines by gas chromatography and electron impact mass spectrometry

The side chain of phenolalkylamines containing a bifunctional group was derivatized as the cyclic boronate, and then the residual phenolic group was trimethylsilylated. The resulting derivatives were single reaction products in each case, with good gas chromatographic properties and informative mass spectra to afford prominent molecular ions by gas chromatography with electron impact mass spectrometry (GC/EI-MS). The cyclic boronated-trimethylsilylated derivatives yielded the isotope pattern for boron ((10)B:(11)B =-1:4.2) and characteristic ions [M](+), [M - H](+), [M - CH(3)](+), [M - RBO](+), [M - TMSO](+), and [M - TMSO - C(6)H(5)](+) ions in the mass spectra. In order to distinguish between m- and p-phenolalkylamines, the mass spectra of the cyclic phenylboronated-trimethylsilylated (PBA-TMS) derivatives were compared with those of the trimethylsilylated (TMS) derivatives. The TMS derivatives of octopamine (p-) and norfenefrine (m-) showed identical mass spectra, while the PBA-TMS derivatives had mass spectra sufficiently different from one other to distinguish between the isomers. The most prominent ion of the PBA-TMS derivative is the [M - H](+) ion (m/z 310) for octopamine and the [M](+) ion (m/z 311) for norfenefrine. Copyright 1999 John Wiley & Sons, Ltd.     

Liquid chromatography/mass spectrometric determination of trans-resveratrol in wine using a tandem solid-phase extraction method

Liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization has been successfully applied to the determination of trans-resveratrol (3,5,4'-trihydroxystilbene) in wine. Of a range of analytical conditions that were tested, optimum results were obtained by the use of reversed-phase high performance liquid chromatography (HPLC) using a mixture of methanol and ammonium acetate as the mobile phase. The negative-ion spectrum of trans-resveratrol showed pseudo-molecular ion, [M - H](-), which was the most abundant ion, and low fragment ions corresponding to the losses of hydroxyl groups of the phenol nucleus. Enhanced selectivity for the separation between trans-resveratrol and endogenous wine constituents was afforded by sample purification with a tandem solid-phase extraction method. The approach permits detection at low concentration of trans-resveratrol. The combination of improved sample pretreatment and an isocratic chromatographic system in conjunction with internal standardization forms the basis of a new assay for the quantitation of trans-resveratrol in wine. Full-scan mass spectra were readily obtained from 8 ng of trans-resveratrol, while a limit of detection of 200 pg (signal-to-noise ratio 3) was attained in the selected ion monitoring mode. The application of LC/MS to the determination of trans-resveratrol in wines is demonstrated by the analysis of red wines. Copyright 1999 John Wiley & Sons, Ltd.     

Mass and double-beta-decay Q value of 136Xe

The atomic mass of 136Xe has been measured by comparing cyclotron frequencies of single ions in a Penning trap. The result, with 1 standard deviation uncertainty, is M(136Xe)=135.907 214 484 (11) u. Combined with previous results for the mass of 136Ba [Audi, Wapstra, and Thibault, Nucl. Phys. A 729, 337 (2003)10.1016/j.nuclphysa.2003.11.003], this gives a Q value (M[136Xe]-M[136Ba])c(2)=2457.83(37) keV, sufficiently precise for ongoing searches for the neutrinoless double-beta decay of 136Xe.     

Role of density imbalance in an interacting bilayer hole system

We study interacting GaAs hole bilayers in the limit of zero interlayer tunneling. When the layers have equal density, we observe a phase-coherent bilayer quantum Hall state (QHS) at a total filling factor nu=1, flanked by a reentrant insulating phase at nearby fillings which suggests the formation of a pinned, bilayer Wigner crystal. As we transfer charge from one layer to another, the phase-coherent QHS becomes stronger, evincing its robustness against charge imbalance, but the insulating phase disappears, suggesting that its stability requires the commensurability of the two layers.     

基于气体放电等离子体射流源的模拟离子引出实验平台物理特性

离子引出过程是原子蒸气激光同位素分离中非常重要的物理过程之一,而其中关键的等离子体参数(等离子体初始密度和电子温度等)均会对离子引出特性产生影响.基于千赫兹电源驱动的氩气高压交流放电等离子体射流源,建立了离子引出模拟实验平台-2015 (IEX-2015),开发了用于诊断氩等离子体参数的"碰撞-辐射"模型,对等离子体射流区的电子温度和电子数密度等关键参数进行了测量.结果表明,电源输入功率和驱动频率以及工作气体流量均会对等离子体射流区的电子温度和数密度产生影响;在真空腔压强为10~(-2)Pa量级下,射流区电子数密度和电子温度的可调参数范围分别为10~9—10~(11)cm~(-3)和1.7—2.8 e V,这与实际离子引出过程中的等离子体参数范围相近.在此基础上,开展了不同引出电压、极板间距和电子数密度条件下初步的离子引出实验,所得到的离子引出电流变化规律亦与实际原子蒸气激光同位素分离中的离子引出特性定性一致.上述研究结果验证了在IEX-2015上开展离子引出模拟实验的可行性,为后续深入开展离子引出特性的实验研究准备了良好的条件.