Identification and Characterization of 4-Hydroxy-2H-1,2-benzothiazine-3-carboxylic Acid 1,1-Dioxide Derivatives by Mass Spectroscopy

Electron impact mass spectral fragmentation of certain esters and amides derived from 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxide is described. Common ions to both series may be observed, as well as others allowing them to be differentiated. The method is promissory for identification and analysis of these compounds.     

On the inter-instrument and the inter-laboratory transferability of a tandem mass spectral reference library. 3. Focus on ion trap and upfront CID

Mass spectral libraries represent versatile tools for the identification of small bioorganic molecules. Libraries based on electron impact spectra are rated robust and transferable. Tandem mass spectral libraries are often considered to work properly only on the instrument that has been used to build the library. An exception from that rule is the 'Wiley Registry of Tandem Mass Spectral Data, MSforID'. In various studies with data sets from different kinds of tandem mass spectrometric instruments, the outstanding sensitivity and robustness of this tandem mass spectral library search approach was demonstrated. The instrumental platforms tested, however, mainly included various tandem-in-space instruments. Herein, the results of a multicenter study with a focus on upfront and tandem-in-time fragmentation are presented. Five laboratories participated and provided fragment ion mass spectra from the following types of mass spectrometers: time-of-flight (TOF), quadrupole-hexapole-TOF, linear ion trap (LIT), 3-D ion trap and LIT-Orbitrap. A total number of 1231 fragment ion mass spectra were collected from 20 test compounds (amiloride, buphenin, cinchocaine, cyclizine, desipramine, dihydroergotamine, dyxirazine, dosulepin, ergotamine, ethambutol, etofylline, mefruside, metoclopramide, phenazone, phentermine, phenytoin, sulfamethoxazole, sulfamoxole, sulthiame and tetracycline) on seven electrospray ionization instruments using 18 different instrumental configurations for fragmentation. For 1222 spectra (99.3%), the correct compound was retrieved as the best matching compound. Classified matches (matches with 'relative average match probability' >40.0) were obtained for 1207 spectra (98.1%). This high percentage of correct identifications clearly supports the hypothesis that the tandem mass spectral library approach tested is a robust and universal identification tool.     

Development of a Fourier-Transform Ion-Cyclotron-Resonance detection for short-lived radionuclides at SHIPTRAP

The Penning-trap mass spectrometer SHIPTRAP at GSI is designed to provide clean and cooled beams of singly charged radioactive ions produced in fusion-evaporation reactions and separated in-flight by the velocity filter SHIP. The scientific goals include mass spectrometry, atomic and nuclear spectroscopy, and chemistry of transuranium species which are not available at ISOL- or fragmentation facilities Penning-trap based mass measurements on radionuclides relies up to now on the destructive time-of-flight ion-cyclotron-resonance method. One of the main limitations to the experimental investigations is the low production rate of most of these exotic nuclides, for which the use of this detection scheme is not applicable. A sensitive and non-destructive method, like the narrow-band Fourier Transform ion-cyclotron-resonance technique, is ideally suited for the identification and characterization of these species. A new cryogenic trap setup for SHIPTRAP exploiting this detection technique as well as some results of first preparatory tests are presented.     

Electron impact mass spectral characteristics and fragmentation pathways of isomeric tetradecadien-1-ols

Characteristics of mass spectra of isomeric tetradecadien-1-ols were investigated by electron impact mass spectrometry, and mass spectral fragmentation pathways were proposed based on collision-induced dissociation experiments and mass-analyzed ion kinetic energy spectrometry. Copyright 1999 John Wiley & Sons, Ltd.     

Schottky mass spectrometry at the heavy ion storage ring ESR

Schottky mass spectrometry is a novel method of precision nuclear mass spectrometry based on the measurement of the revolution frequencies of cooled ions in storage rings performed by non-destructive frequency analysis of the beam noise, the well-established Schottky diagnosis technique. The method was applied for the first time at the Experimental Storage Ring ESR at GSI observing electron cooled highly charged ions up to bare nuclei at relativistic energies around several hundred MeV/u. To demonstrate the performance and feasibility of the method at the ESR, experimental tests have been carried out using beams of nuclear fragments produced in the ring itself by the interaction of different primary beams with the internal gas jet target. Futhermore, first Schottky mass measurements of secondary nuclear beams produced by projectile fragmentation of Au and Bi primary beams in a thick Be-target were carried out in order to determine the masses for numerous heavy neutron deficient nuclei which had not been measured before. Relative accuracies for the measured mass values in the order of 1×10^–6 and below can be achieved. The method is briefly discussed and some early results are presented.     

Identification of phototransformation products of sildenafil (Viagra) and its N-demethylated human metabolite under simulated sunlight

Recent publications on pharmaceutical monitoring are increasingly covering the field of illicit drugs and lately the forensic evaluation of designing illegal analogs of lifestyle drugs like the phosphodiesterase type 5 (PDE-5) inhibitors Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). Recently, the presence of all three erectile dysfunction treatment drugs has been reported in wastewaters at very low concentrations. In the environment, contaminants undergo various physical or chemical processes classified into abiotic (photolysis, hydrolysis) and biotic (biodegradation) reactions. Thus, changes in the chemical structure lead to the formation of new transformation products, which may persist in the environment or be further degraded. This study describes the photolysis of sildenafil (SDF) and its human metabolite N-demethylsildenafil (DM-SDF) under simulated solar radiation (Xenon lamp). Following chromatographic separation of the irradiated samples, eight photoproducts in the SDF samples and six photoproducts for DM-SDF were detected and characterized. The combination of ultra performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QToF-MS), liquid chromatography-atmospheric pressure chemical ionization-triple quadrupole mass spectrometry (LC-APCI-QqQ-MS) and hydrogen/deuterium-exchange experiments allowed to propose plausible chemical structures for the photoproducts, taking into account the characteristic fragmentation patterns and the accurate mass measurements. These mass spectral data provided sound evidence for the susceptibility of the piperazine ring toward photodegradation. A gradual breakdown of this heterocyclic structure gave rise to a series of products, which in part were identical for SDF and DM-SDF. The sulfonic acid, as the formal product of sulfonamide hydrolysis, was identified as key intermediate in the photolysis pathway. In both drug/metabolite molecules, phototransformation processes taking place beyond the sulfonamide group were deemed to be of minor relevance.     

Identification of new flavan-3-ol monoglycosides by UHPLC-ESI-Q-TOF in grapes and wine

Flavan-3-ol monoglycosides, having four aglycons (+)-catechin, (-)-epicatechin, (-)-epigallocatechin and epicatechin gallate monomeric units, are detected for the first time in Vitis vinifera L. cv. Merlot grape seeds and wine. These compounds were analyzed in red wine, seed and skin extracts by electrospray ionization quadrupole time of flight mass spectrometry (MS) in negative mode. Fragment ions derived from retro-Diels Alder, heterocyclic ring fragmentation, benzofuran forming fragmentation and glycoside fragmentations were detected in targeted MS/MS mode. These compounds were not detected in skins; the comparative study showed evidence that these glycosylated compounds originate only from grape seeds. Our method allows for the identification of these glycosylated compounds based on their exact mass and their specific fragmentation pattern. However, exact glucose position on the monomeric units can not be determined. This work allowed us to partially identify 14 new flavan-3-ol monoglycosides, based on the exact mass of the molecular ions and their specific retro-Diels Alder, heterocyclic ring fragmentation, benzofuran forming fragmentation and glycoside fragmentations.     

琅琊山区主要树种冠层光谱年际变化研究

森林树木的生理机制和生态结构随年份变化,该变化通过其冠层光谱特征在一定程度上有规律的表现出来。掌握森林树木光谱特征随年份变化的规律,既有利于遥感解译,也为多树种的识别与分类、生物化学成分估测等提供一定的科学依据。本研究利用高分辨率光谱仪对研究区7个主要落叶树种和7个主要常绿树种的不同年份冠层光谱特征进行测量,分别获取4个不同年龄段的光谱曲线,并计算出一阶导数曲线,从而深入分析不同落叶树种、不同常绿树种在不同年份和相同年份的光谱特征变化规律,比较各树种在可见光波段和近红外波段的光谱差异变化,以找出最适宜多树种识别的最佳年份和最佳波段。结果显示：落叶树种和常绿树种的冠层光谱特征随年份变化表现出一定的规律性,光谱反射率随年龄增加而升高;光谱变化差异均在近红外波段最为明显,此波段是进行多树种识别的最佳波段。     

Chemical Profiling of an Indian Herbal Formula Using Liquid Chromatography Coupled with Electro Spray Ionization Mass Spectrometry

Amruthotharam kashayam is an important Ayurvedic formulation prepared using specified plant parts of Tinospora cordifolia, Terminalia chebula, and Zingiber officinale. The current study developed a rapid liquid chromatographic method coupled with electro spray ionization mass spectrometry for the identification of major phytoconstituents present in the formulation. Reverse phase high-pressure liquid chromatogram was developed as chemical fingerprint. The mass spectrum along with the MS/MS fragmentation on collision-induced dissociation led to the structural identification of separated compounds. Phenolic acids such as quinic acid, protocatechuic acid, gallic acid, and chebulic acid were identified in the formulation along with some flavonoids.     

Formation of oligomeric alkenylperoxides during the oxidation of unsaturated fatty acids: an electrospray ionization tandem mass spectrometry study

This study reports the identification of oligomeric alkenylperoxides by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS(2)), during the oxidation of oleic, linoleic and linolenic acids with Fenton's (Fe(2+)/H(2)O(2)) and Fe(2+)/O(2) systems. The reactions were followed by ferrous oxidation-xylenol orange method together with GC-MS and GC-FID, allowing to observe that both oxidation systems are different in terms of hydroperoxide evolution, probably due to the presence of different intermediate reactive species: perferryl ion and OH(·) radical responsible for the decomposition of lipid hydroperoxides and formation of new compounds. The analysis of ESI-MS in the negative mode, obtained after oxidation of each fatty acid, confirmed the presence of the monomeric oxidation products together with other compounds at high mass region above m/z 550. These new ions were attributed to oligomeric structures, identified by the fragmentation pathways observed in the tandem mass spectra.     

GC-MS of amaryllidaceous galanthamine-type alkaloids

Galanthamine-type alkaloids produced by plants of the Amaryllidaceae family are potent acetylcholinesterase inhibitors. One of them, galanthamine, has been marketed as a hydrobromide salt for the treatment of Alzheimer's disease. In the present work, gas chromatography with electron impact mass spectrometry (GC-EIMS) fragmentation of 12 reference compounds isolated from various amaryllidaceous plants and identified by spectroscopic methods (1D and 2D nuclear magnetic resonance, circular dichroism, high-resolution MS (HRMS) and EIMS) was studied by tandem mass spectrometry (GC-MS/MS) and accurate mass measurements (GC-HRMS). The studied compounds showed good peak shape and efficient GC separation with a GC-MS fragmentation pattern similar to that obtained by direct insertion probe. With the exception of galanthamine-N-oxide and N-formylnorgalanthamine, the galanthamine-type compounds showed abundant [M](+.) and [M-H](+) ions. A typical fragmentation pattern was also observed, depending on the substituents of the skeleton. Based on the fragmentation pathways of reference compounds, three other galanthamine-type alkaloids, including 3-O-(2'-butenoyl)sanguinine, which possesses a previously unelucidated structure, were identified in Leucojum aestivum ssp. pulchelum, a species endemic to the Balearic islands. GC-MS can be successfully applied to Amaryllidaceae plant samples in the routine screening for potentially new or known bioactive molecules, chemotaxonomy, biodiversity and identification of impurities in pharmaceutical substances. Copyright ? 2012 John Wiley & Sons, Ltd.     

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。     

Analytics/Methods

An overview is presented of biomedical applications of stable isotopes in general, but mainly focused on the activities of the Center for Liver, Digestive and Metabolic Diseases of the University Medical Center Groningen. The aims of metabolic studies in the areas of glucose, fat, cholesterol and protein metabolism are briefly explained, as well as the principle of breath testing and the techniques to study body composition and energy expenditure. Much attention is paid to the analytical considerations based upon metabolite concentrations, sample size restrictions, the availability of stable isotope labelled substrates and dose requirements in relation to compound-specific isotope analysis. The instrumental advantages and limitations of the generally used techniques gas chromatography/reaction/isotope ratio mass spectrometry and gas chromatography/mass spectrometry are described as well as the novelties of the recently commercialised liquid chromatography/combustion/isotope ratio mass spectrometry. The present use and future perspective of infrared (IR) spectrometry for clinical and biomedical stable isotope applications are reviewed. In this respect, the analytical demands on IR spectrometry are discussed to enable replacement of isotope ratio mass spectrometry by IR spectrometry, in particular, for the purpose of compound-specific isotope ratio analysis in biological matrices.     

Determination of levamisole in feeds by liquid chromatography coupled to electrospray mass spectrometry on an ion trap

Test methods have to be developed by laboratories for official control to monitor possible misuse of veterinary drugs in animal productions, also through feeding stuff. A novel method for identification and quantification of levamisole in feeds by liquid chromatography coupled to electrospray mass spectrometry in an ion trap (LC/ESI-MS/MS) is herein described; after a single-step cleanup by liquid-liquid extraction from the feed and separation by reversed-phase liquid chromatography, levamisole was determined and unambiguously confirmed by tandem mass spectrometry, on the basis of two product ions. The method was in-house validated, according to the Regulation 882/2004/EC, evaluating trueness, repeatability, within-laboratory reproducibility, ruggedness, specificity, and the limit of quantification (LOQ). The method is reliable and specific for complete and complementary feeds for pigs, cattle, rabbits and poultry; very good mean recoveries (higher than 92 %) and precision (RSD values?相似文献   

Analytical techniques in biomedical stable isotope applications: (isotope ratio) mass spectrometry or infrared spectrometry?

An overview is presented of biomedical applications of stable isotopes in general, but mainly focused on the activities of the Center for Liver, Digestive and Metabolic Diseases of the University Medical Center Groningen. The aims of metabolic studies in the areas of glucose, fat, cholesterol and protein metabolism are briefly explained, as well as the principle of breath testing and the techniques to study body composition and energy expenditure. Much attention is paid to the analytical considerations based upon metabolite concentrations, sample size restrictions, the availability of stable isotope labelled substrates and dose requirements in relation to compound-specific isotope analysis. The instrumental advantages and limitations of the generally used techniques gas chromatography/reaction/isotope ratio mass spectrometry and gas chromatography/mass spectrometry are described as well as the novelties of the recently commercialised liquid chromatography/combustion/isotope ratio mass spectrometry. The present use and future perspective of infrared (IR) spectrometry for clinical and biomedical stable isotope applications are reviewed. In this respect, the analytical demands on IR spectrometry are discussed to enable replacement of isotope ratio mass spectrometry by IR spectrometry, in particular, for the purpose of compound-specific isotope ratio analysis in biological matrices.     

近红外光谱的不同产地柑橘无损鉴别方法

柑橘是世界第一大水果。不同产地的柑橘内部品质和价格有所不同,但其外观差别较小,外行人较难通过肉眼实现准确鉴别分析。DNA标记法与仪器分析操作复杂、成本较高,且对样品具有破坏性,无法实现快速无损分析,影响了产品的二次销售。近红外光谱技术是一种快速无损的新型检测手段,可以用于不同产地农产品的鉴别分析。由于柑橘皮对光谱的干扰较大,导致现阶段柑橘产地无损鉴别研究匮乏。此外柑橘体积较大,因此需要对光谱采样点进行优化。为此,基于近红外光谱技术与化学计量学方法,提出了一种用于不同产地柑橘无损鉴别的新方法。使用近红外光谱仪得到了120个来自云南、湖南、广西武鸣、广西来宾的沃柑漫反射光谱数据。采用单一和组合光谱预处理方式以消除光谱中的多种干扰;采用主成分分析方法对数据进行降维处理,并以此作为输入值结合Fisher线性判别分析方法构建柑橘产地鉴别模型,并与主成分分析模型进行对比。此外,考察了不同光谱采样位置（赤道线4个采集点、果梗部以及果顶部）对结果的影响。结果表明：主成分分析方法结合优化光谱预处理的方法不能实现不同产地柑橘的准确鉴别分析,最优鉴别率仅为5%;而采用主成分分析-Fisher线性判别分析方法,利用赤道线4个点的平均光谱结合去偏置校正或多元散射校正预处理方法可实现不同产地柑橘的100%鉴别分析;采用主成分分析-Fisher线性判别分析对6个点的平均光谱数据进行处理时,采用原始光谱便可实现不同产地柑橘的100%鉴别分析。为此,通过对光谱预处理方法以及光谱采集点的优化,利用主成分分析-Fisher线性判别分析方法即可建立准确的柑橘产地鉴别模型,为不同产地柑橘的快速鉴别提供了新途径,为后续各种柑橘类水果的鉴别分析提供了参考。     

基于叶片反射光谱特征的银杏健康量化评价技术

准确地诊断树木健康状况是城市森林树木管理工作的基础,也是目前生产中急需的技术。通过土壤和植物养分分析诊断树木健康可靠性差,通过形态特征调查诊断树木健康费时、费力,如何快速、准确、无损地诊断树木健康已经成为城市树木健康管理的重要技术瓶颈。以北京市银杏为研究对象,对基于叶片反射光谱特征的树木健康诊断技术进行了研究。通过13个外貌形态特征聚类将树木健康划分成健康木、亚健康木、一般健康木和不健康木4个等级,不同健康等级树木叶片色素含量差异极其显著(p<0.001) ,因叶绿素含量与光谱反射率之间存在相关关系,所以采用叶片反射光谱特征判断树木健康状况是可行的。采用因子分析法,通过15个叶片反射光谱指标构建了能够综合反映叶片反射光谱特征的绿度指数、色素指数、三边指数。不同健康等级间叶片反射光谱指标以及三个反射光谱指数均有极显著差异(p<0.001)。所以,采用三个反射光谱指数构建了银杏健康评价的多元二次模型,经检验模型预测精度达到79%,可以作为银杏树木健康快速诊断。选取的光谱指标较为全面,方法简洁,并通过综合分析,确定了不同健康等级树木核心形态指标以及叶片的绿度指数、色素指数、三边指数等综合得分以及得分范围,为生产中直接使用该方法诊断银杏健康状况提供了标准。     

Short TE in vivo (1)H MR spectroscopic imaging at 1.5 T: acquisition and automated spectral analysis

Spectral analysis of short TE in vivo proton magnetic resonance spectroscopic imaging (MRSI) data are complicated by the presence of spectral overlap, low signal to noise and uncharacterized signal contributions. In this study, it is shown that an automated data analysis method can be used to generate metabolite images from MRSI data obtained from human brain at TE = 25 ms and 1.5 T when optimized pulse sequences and a priori metabolite knowledge are used. The analysis approach made use of computer simulation methods to obtain a priori spectral information of the metabolites of interest and utilized a combination of parametric spectral modeling and non-parametric signal characterization for baseline fitting. This approach was applied to data from optimized PRESS-SI and multi-slice spin-echo SI acquisitions, for which sample spectra and metabolite images are shown.     

小兴安岭主要树种冠层光谱季相变化研究

森林每年随季节变化而出现形态和生理机能的规律性变化,该变化在一定程度通过其光谱特征有规律地展现。准确地掌握森林冠层光谱特征随季节变化的规律不仅是遥感解译的关键,也为树种识别、动态监测和生化参数反演提供理论基础。利用地物光谱仪对研究区9个主要树种的冠层光谱数据进行长期观测,获取了春夏秋冬四个季节的反射光谱曲线并生成一阶导数曲线,同时还计算了常用的植被特征参数,进而分析不同树种在相同季相和不同季相的光谱特征,对比不同树种在可见光和近红外波段的季相变化特征和差异,探索遥感手段用于树种分类识别的最佳波段、最佳时相。结果表明：不同树种在各生长季光谱具有独特的特征,落叶树种光谱特征因季节的改变而呈现有规律的变化, 而常绿树种光谱特征年变化不明显。光谱特征的变化有效地反应了物候的变化,应用多季相的数据进行分类可以取得最好的效果,常绿树种和落叶树种光谱特征在冬季差异明显,而夏季是采用单季相遥感数据进行树种识别的最佳时节。