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Km,Vmax和Kcat分别为8.4×10-5mol· L-1,7.4×10-6mol·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△F(F0-F)与青蒿素浓度在0.0～1.27×10-6mol·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.