Search

Glycans are molecules that contain multiple monosaccharides linked by glycosidic bonds and often bind to proteins or lipids to form various glycoconjugates. Rising awareness of the vital role that glycosylation plays in protein functioning governs the need for further advances in glycan analysis. Because free glycans lack chromophore or fluorophore properties, and do not ionize well, they are often derivatized, to facilitate their separation or detection, and to enhance the sensitivity of the analysis. Released glycans are usually derivatized using a fluorescent tag, which enables their optical detection in LC profiling. Some fluorescent labels can also improve ionization efficiency, which then facilitates MS detection. For this reason, there is a need to design fluorophores that will contribute more to the fluorescence and ionization of glycans and the need to quantify these contributions to improve glycan analysis methods in negative MS mode as these methods are more informative than methods involving positive MS mode, allowing for a less ambiguous elucidation of detailed glycan structures. Therefore, eleven fluorescent labels of different chemo-physical properties were chosen in order to study the influence of label hydrophobicity and presence of a negative charge on glycan ionization in negative MS mode. N-glycans released from IgG sample were labeled with one of the eleven labels, purified with HILIC-SPE and analyzed with HILIC-UHPLC-FLR- MS. The results show that hydrophobicity significantly contributes more to signal-to-noise intensity ratios in the mass spectrum than the negative ion charge in the case of negative MS mode. With this in mind, further research and development of fluorophores that will be suitable for glycan analysis in the negative MS mode are proposed.

The search for suitable ion mobility spectrometry (IMS) calibrant compounds is ongoing and necessitates the use of highly accurate reduced ion mobility (K0) values across a range of instrumental conditions. Such values will be used in calibrating devices to shift the ion mobility scales and alarm windows for chemicals of interest to their proper locations based on the instrumental conditions present during calibration and sampling. Many positive ion mode calibrants have been investigated, whereas investigations for a negative ion detection mode calibrant have been more limited. Isoflurane (IsoF) is a strong candidate as a negative ion mode calibrant. This report documents the accurately measured K0 values for IsoF product ions as a function of multiple instrumental parameters. K0 values were measured in two instrumentation modes as a function of drift gas temperature, water concentration, and dopant concentration. This report culminates with our evaluation of the suitability of IsoF as a negative ion mode calibrant for IMS applications.

The main goal of the present research is to check the suitability of the well-known brittle fracture criterion, namely the averaged strain energy density (ASED), in predicting mixed mode I/II brittle fracture of round V notches under negative mode I conditions. For this purpose, it is attempted for the first time to theoretically predict the fracture loads of numerous round-tip V-notched Brazilian disk (RV-BD) specimens made of PMMA and subjected to mixed mode I/II loading with negative mode I contributions that have been most recently reported in the open literature. It is revealed that ASED criterion is suitable for brittle fracture prediction not only under conventional mixed mode I/II loading conditions, but also under mixed mode I/II loading with negative mode I contributions.

High-performance liquid chromatography hyphenated with tandem mass spectrometry (LC–MS/MS) was used to analyze a 76-year-old injection preparation of neosalvarsan. The sample constituents were separated on the reverse phase C18 by the optimized gradient elution of methanol and water. Using electrospray ionization in the negative mode (ESI−), the complete disintegration of neosalvarsan was proved. The structures of two degradation products of neosalvarsan, which are 2-(hydroxymethylamino)-4-arsenosophenol and As-(3-amino-4-hydroxyphenyl)arsonous acid were identified by MS2, and the ESI− fragmentation mechanism was proposed.

Drift tube ion mobility spectrometry with a novel atmospheric electron emission (AEE) source was developed for determination of gaseous and blister chemical warfare agents (CWAs) in negative mode. The AEE source was fabricated from an aluminum substrate electrode covered with 1 μm silver nanoparticle-dispersed silicone resin and a thin gold layer. This structure enabled stable tunneling electron emission upon the application of more than 11 V potential under atmospheric pressure. The reactant ion peak (RIP) was observed for the reduced mobility constant ( K

Commercial off-the-shelf (COTS) ion mobility spectrometers (IMS) are widely used for the trace detection of drugs and explosives in security applications and are designed to be operated by non-technical users. In non-technical user mode, the detection algorithm of the COTS IMS evaluates the sample data against the programmed parameters for a specific and limited list of target substances, and reports if any of the programmed target substances are detected. The simplicity in operation is offset by the loss of analytical information available from the spectral details. In this work, we present for the first time a COTS IMS being operated in technical user mode in the field, analyzing packages selected for customs examination. The COTS IMS was used in combination with a Fourier transform infrared (FTIR) spectrometer to evaluate the effectiveness of presumptive field testing. Three case studies are presented to demonstrate the usefulness of operating COTS IMS in technical user mode: to corroborate results obtained from the FTIR, to indicate the presence of unprogrammed substances, and to indicate the presence of substances in minor to trace amounts that were not identified by the FTIR. This work also demonstrates the use of IMS in negative mode to identify the citrate salt form of a drug.

In an investigation into the historical use of various plant species as herbal teas in South Africa and the commercialization of rooibos (Aspalathus linearis), 37 tea samples from a depository of 1933 were analysed. These samples are known as the Nortier collection and were put in the depository by Benjamin Ginsberg. Nortier and Ginsberg were instrumental in the commercialisation of Rooibos tea. Liquid-chromatography–high resolution mass spectrometry (LC–HRMS) was used with electrospray ionisation (ESI) in negative mode to compare the flavonoids and phenolic acids and identify marker compounds in the samples. The positively identified marker compounds together with multivariate data tools were used to distinguish between the different teas and group similar ones together. The LC–HRMS chromatogram of the 1933 Nortier tea, the tea from which cultivated rooibos emanated, is virtually identical to a commercial cultivated tea from 2016. The selection of teas is an interesting look into the history of herbal tea in South Africa, the species used and the decision-making process of Nortier in developing the industry. The historic “reed tea” (riettee) was identified for the first time as Thesium macrostachyum and other Thesium species and is the same as the tea that is still used in the Wupperthal area as “lidjiestee”.

In this study, two monophasic isopropanol-water mixtures (IPA:H2O 75:25 v/v and IPA:H2O 90:10 v/v) were compared with traditionally employed biphasic methods of Bligh & Dyer and Matyash et al. as extraction systems for lipidomics analysis in Hela cells. Samples were analyzed by UHPLC-ESI-QTOF-MS/MS in positive and negative mode using sequential window acquisition of all theoretical fragment ion spectra (SWATH) and a relatively new software (MS-DIAL) was employed for the processing of the data which includes detection of peaks, MS/MS spectra deconvolution, identification of detected lipids and alignment of peaks through the analyzed samples. The studied performance parameters such as precision, recoveries of isotopically labeled internal standards and endogenous lipids, number of extracted lipids, and complexity of employed procedure showed that extraction with IPA:H2O 90:10 v/v performs similar to the Matyash protocol and better than Bligh & Dyer as well as IPA:H2O 75:25 v/v. However, less complex monophasic protocol which is simpler to implement and can be executed in plastic rather than glass, make the monophasic IPA:H2O 90:10 v/v protocol an excellent alternative to the classical biphasic protocols for reversed phase LC-MS lipidomics studies.

Background It is essential to identify the chemical components for the quality control methods establishment of Chinese Classical Formula (CCF). However, CCF are complex mixture of several herbal medicines with huge number of different compounds and they are not equal to the combination of chemical components from each herb due to particular formula ratio and preparation techniques. Therefore, it is time-consuming to identify compounds in a CCF by analyzing the LC–MS/MS data one by one, especially for unknown components. Methods An ultra-high pressure liquid chromatography-linear ion trap-orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS) approach was developed to comprehensively profile and characterize multi-components in CCF with Erdong decoction composed of eight herbal medicines as an example. Then the MS data of Erdong decoction was analyzed by MS/MS-based molecular networking and these compounds with similar structures were connected to each other into a cluster in the network map. Then the unknown compounds connected to known compounds in a cluster of the network map were identified due to their similar structures. Results Based on the clusters of the molecular networking, 113 compounds were rapidly tentative identification from Erdong decoction for the first time in the negative mode, which including steroidal saponins, triterpenoid saponins, flavonoid O-glycosides and flavonoid C-glycosides. In addition, 10 alkaloids were tentatively identified in the positive mode from Nelumbinis folium by comparison with literatures. Conclusion MS/MS-based molecular networking technique is very useful for the rapid identification of components in CCF. In Erdong decoction, this method was very suitable for the identification of major steroidal saponins, triterpenoid saponins, and flavonoid C-glycosides.

This publication describes the detection of buried defects in 3D NAND flash. Although not electrically active, they are a reliability risk and therefore detection is very important for process improvement. Negative mode electron beam inspection must be used to activate and detect these defects. Negative mode is able to generate a higher electrical field compared to conventional positive mode, sufficient to break through the damaged insulator making the defects electrically active and detectable. Negative mode inspection also makes the defects visible to electrical test, which is not the case when positive mode inspection is used. Further investigation shows that the breakthrough activates only pre-existing defects and does not affect healthy blocks.

Chia, flax, and sesame seeds are well known for their nutritional quality and are commonly included in bakery products. So far, the development of methods to verify their presence and authenticity in foods is a requisite and a raised need. In this work we applied untargeted metabolomics to propose authenticity markers. Seeds were analyzed by HPLC-MS/MS and 9938 features in negative mode and 9044 in positive mode were obtained by Mzmine. After isotopes grouping, alignment, gap-filling, filtering adducts, and normalization, PCA was applied to explore the dataset and recognize pre-existent classification patterns. OPLS-DA analysis and S-Plots were used as supervised methods. Twenty-five molecules (12 in negative mode and 13 in positive mode) were selected as discriminant for the three seeds, polyphenols and lignans were identified among them. To the best of our knowledge, this is the first approach using non-target HPLC-MS/MS for the authentication of chia, flax and sesame seeds.

Physical review / D 104(9), 096009 (1-13) (2021). doi:10.1103/PhysRevD.104.096009, We study negative modes around the Coleman���de Luccia bounce solution. The conditions for the appearance of an infinite number of negative modes do not coincide between Lagrangian and Hamiltonian formulations in the literature, and we discuss the origin of this difference in detail. We show how different choices of the variable for the fluctuation around the bounce solution affect the negative mode condition in the Hamiltonian approach, and point out that there exists a choice that gives the same negative mode condition as the Lagrangian approach., Published by Inst., Melville, NY

Using structures of subwavelength metallic capped helices with both negative electric and magnetic couplings, we demonstrate a broadband negative mode index metasurface. Numerical and experimental results are presented for the structure with negative dispersion bandwidth of 44% compared to the resonant frequency of individual capped helices. Optimisation of such structures in terms of their size, element geometry and operational passband width is demonstrated.

Electrospray ionization (ESI) operating in the negative mode coupled to high-resolution mass spectrometry is the most popular technique for the characterization of dissolved organic matter (DOM). The vast molecular heterogeneity and the functional group diversity of this complex mixture prevents the efficient ionization of the organic material by a single ionization source, so the presence of uncharacterized material is unavoidable. The extent of this poorly ionizable pool of carbon is unknown, is presumably variable between samples, and can only be assessed by the combination of analysis with a uniform detection method. Charged aerosol detection (CAD), whose response is proportional to the amount of nonvolatile material and is independent from the physicochemical properties of the analytes, is a suitable candidate. In this study, a fulvic acid mixture was fractionated and analyzed by high-pressure liquid chromatography–mass spectrometry in order to investigate the polarity and size distributions of highly and poorly ionizable material in the sample. Additionally, DOM samples of terrestrial and marine origins were analyzed to evaluate the variability of these pools across the land–sea aquatic continuum. The relative response factor values indicated that highly ionizable components of aquatic DOM mixtures are more hydrophilic and have lower molecular weight than poorly ionizable components. Additionally, a discrepancy between the samples of terrestrial and marine origins was found, indicating that marine samples are better represented by ESI than terrestrial samples, which have an abundant portion of hydrophobic poorly ionizable material. Title in thesis list of papers: Investigating the ionisation of dissolved organic matter by electrospray ionisation

Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved. Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled. To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode. Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself. Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites. Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments. Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.

A rapid analytical method using supercritical fluid chromatography (SFC) coupled to mass spectrometry for the simultaneous identification and determination of eleven tyrosine kinase inhibitors (TKIs) was developed and validated. For quantitative assay, a tested solution with a high concentration of 0.4 mg mL−1 was applied for SFC determination. For identification purposes, a diluted solution with a concentration down to 1 μg mL−1 was introduced into a SFC-MS system to gain confirmative information. Six different columns were examined in this study and the best separation was achieved on an Acquity UPC2 Torus DIOL column (3.0 mm × 100 mm, 1.7 μm) using a gradient program. The effects of different additives, column temperature and back pressure were investigated. Negative and positive modes were compared using Xevo G2-XS QTOF after SFC separation. The results showed that the response of TKIs in positive mode was much higher than that in negative mode and thus positive mode was adopted. The method validation was performed in the concentration range of 1–600 μg mL−1 for all TKIs with a coefficient of determination (R2) greater than 0.9995. The developed method was applied to several samples collected from the market. Two out of them in powder form were identified to be afatinib with a content of 0.94 mg mg−1 and osimertinib with a content of 0.92 mg mg−1. Another sample in capsule form was identified to be osimertinib with a content of 57 mg per capsule.

Glycosaminoglycans (GAGs) are polysaccharides produced by most mammalian cells and involved in a variety of biological processes. However, due to the size and complexity of GAGs, detailed knowledge about the structure and expression of GAGs by cells, the glycosaminoglycome, is lacking. Here we report a straightforward and versatile approach for structural domain mapping of complex mixtures of GAGs, GAGDoMa. The approach is based on orthogonal enzymatic depolymerization of the GAGs to generate internal, terminating, and initiating domains, and nanoflow reversed-phase ion-pairing chromatography with negative mode higher-energy collision dissociation (HCD) tandem mass spectrometry (MS/MS) for structural characterization of the individual domains. GAGDoMa provides a detailed structural insight into the glycosaminoglycome, and offers an important tool for deciphering the complexity of GAGs in cellular physiology and pathology.

Naphthenic acids (NAs) constitute one of the toxic components of the produced water (PW) from offshore oil platforms discharged into the marine environment. We employed liquid chromatography (LC) coupled to high-resolution mass spectrometry with electrospray ionization (ESI) in negative mode for the comprehensive chemical characterization and quantification of NAs in PW samples from six different Norwegian offshore oil platforms. In total, we detected 55 unique NA isomer groups, out of the 181 screened homologous groups, across all tested samples. The frequency of detected NAs in the samples varied between 14 and 44 isomer groups. Principal component analysis (PCA) indicated a clear distinction of the PW from the tested platforms based on the distribution of NAs in these samples. The averaged total concentration of NAs varied between 6 and 56 mg L-1, among the tested platforms, whereas the concentrations of the individual NA isomer groups ranged between 0.2 and 44 mg L-1. Based on both the distribution and the concentration of NAs in the samples, the C8H14O2 isomer group appeared to be a reasonable indicator of the presence and the total concentration of NAs in the samples with a Pearson correlation coefficient of 0.89.

The characterization of plant compounds with pharmacological activity is a field of great relevance in research and development. As such, identification techniques with the goal of developing new drugs or even validating the bioactive properties of extracts must be explored in order to further expand the knowledge of plant extract composition. Most works in this field employ HPLC, when exploring non-structural and cell wall carbohydrates from Rhynchelytrum repens. Phenolic compounds were studied by classical chromatography techniques and UV-vis spectrophotometry, with C-glycosylated flavonoids being detected but with no further details regarding the chemical structure of these compounds. In this work we employ paper spray ionization mass spectrometry (PS-MS) for the evaluation of the chemical profile of R. repens methanol extract. Positive ionization mode identified 15 compounds, belonging to flavonoids, fatty acids, and other classes of compounds; negative mode ionization was able to identify 20 compounds comprising the classes of quinic acids, stilbenes and flavonoids. PS-MS proved effective for the evaluation of R. repens extracts, making it possible to identify a total of thirty-five compounds. The bioactive properties attributed to R. repens were confirmed by the identification and characterization of compounds identified by PS-MS.

Introduction Ilex pubescens Hook et Arn mainly contains triterpenoids that possess antithrombotic, anti-inflammatory and analgesic effects. Quantitative and qualitative analyses of the triterpenoids in I. pubescens can be useful for determining the authenticity and quality of raw materials and guiding its clinical preparation. Objectives To establish a method for rapid and comprehensive analysis of triterpenoids in I. pubescens using ultra-high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS), which will also be applied to evaluate the contents of nine triterpenoids among root, root heartwood and root bark of I. pubescens to judge the value of the root bark to avoid wastage. Methods UPLC-ESI-QTOF-MS data from the extracts of I. pubescens in negative mode were analysed using Peakview and Masterview software that provided molecular weight, mass errors, isotope pattern fit and MS/MS fragments for the identification of triterpenoids. The quantification of nine investigated compounds of I. pubescens was accomplished using MultiQuant software. Results A total of 33 triterpenoids, five phenolic acids, two lignans and a flavonol were characterised in only 14 min. The total content of the nine compounds in the root bark was generally slightly higher than that of the root and root heartwood, which has not been reported before. Conclusion The developed UPLC-ESI-QTOF-MS method was proven to be rapid and comprehensive for simultaneous qualitative and quantitative analyses of the characteristic triterpenoids in I. pubescens. The results may provide a basis for holistic quality control and metabolic studies of I. pubescens, as well as serve as a reference for the analysis of other Ilex plants. Copyright © 2017 John Wiley & Sons, Ltd.

A sensitive method to simultaneously quantitate chlorpyrifos, chlorpyrifos oxon and the detoxified product 3,5,6-trichloro-2-pyridinol (TCP) was developed using either liquid-liquid extraction for culture media samples, or protein precipitation for cell samples. Multiple reaction monitoring in positive ion mode was applied for the detection of chlorpyrifos and chlorpyrifos oxon, and selected ion recording in negative mode was applied to detect TCP. The method provided linear ranges from 5 to 500, 0.2-20 and 20-2000ng/mL for media samples and from 0.5-50, 0.02-2 and 2-200ng/million cells for CPF, CPO and TCP, respectively. The method was validated using selectivity, linearity, precision, accuracy, recovery, stability and dilution tests. All relative standard deviations (RSDs) and relative errors (REs) for QC samples were within 15% (except for LLOQ, within 20%). This method has been successfully applied to study the neurotoxicity and metabolism of chlorpyrifos in a human neuronal model.

In this paper, first the fracture load, the crack initiation angle and the crack trajectory are experimentally measured for the round-tip V-notched Brazilian disk specimen made of polymethyl-methacrylate under compressive-shear loading. Then, the fracture load and the crack initiation angle are predicted by using the extended finite element method on the basis of the linear cohesive crack criterion. The fracture trajectory of the round-tip V-notched Brazilian disk specimens is also estimated by means of the extended finite element method and the incremental methods. Both the experimental observations and the theoretical fracture models indicate that although the notch bisector line is under compressive-shear loading, one half of the notch border still sustains tensile stresses and fracture takes place from this half. A very good agreement is shown to exist between the theoretical predictions and the experimental results for various notch opening angles and different notch radii.

Diagnosis and treatment of inborn errors of metabolism (IEM) require the analysis of a variety of metabolites. These compounds are usually quantified by targeted platforms. High resolution mass spectrometry (HRMS) has the potential to detect hundreds to thousands of metabolites simultaneously. A chip-based nanoelectrospray source (chip-based nanoESI) enables the direct infusion of biological samples. Major advantages of this system include high sample throughput, no sample carryover, and low sample consumption. The combination, chip-based nanoESI-HRMS enables untargeted metabolomics of biological samples but its potential for quantification of metabolites has not been reported. We investigated whether chip-based nanoESI-HRMS is suitable for quantification of metabolites in dried blood spots (DBS). After addition of internal standards, metabolites were extracted with methanol. Aliquots of each extract were analysed by chip-based nanoESI-HRMS operating in both positive and negative mode with an m/z window of 70-600 and a resolution of 140,000. Total run time was 4.5 min per sample and a full report could be generated within 40 min. Concentrations of all 21 investigated diagnostic metabolites in DBS as quantified by chip-based nanoESI-HRMS correlated well with those obtained by targeted liquid chromatography-tandem mass spectrometry. We conclude that chip-based nanoESI-HRMS is suitable for quantification.

Ultra high performance liquid chromatography coupled with mass spectrometry and combining a tissue-smashing extraction technique was developed for the simultaneous quantitative analysis of 12 compounds in the roots of Pulsatilla chinensis. Among them, compound 6 was characterized and accurately quantified in this herb for the first time. The parameters of extraction condition were simultaneously optimized with a Box-Behnken design and Derringer's function. The optimized conditions were as follows: sample quantity of 0.5 g, ethanol concentration of 70%, and extraction time of 200 s. Multiple-reaction monitoring scanning was employed for the quantification between positive and negative mode in a single run of 6 min. Full validation of the method was carried out, and the results indicated that the method was rapid, specific, and reliable. The developed method was successfully applied to quantify the 12 compounds in 33 batches of P. chinensis from different provinces. Moreover, the principal component analysis was performed to compare the P. chinensis collected from different provinces of China based on quantitative data and the results indicated that the content of compounds could be used to differentiate the origins of P. chinensis. These results demonstrated that this method is feasible and reliable for the quality control of P. chinensis.

This work reports the theoretical and experimental study of fragmentation reactions in the gas phase of five phenolic acids using triple quadrupole mass spectrometry by electrospray ionization in negative ionic mode, as well as the isotope exchange experiments. MS/MS spectra were analyzed to suggest the fragmentation mechanisms, while theoretical calculations at the theory level B3LYP/6-311+G** were performed to expose the proposed mechanisms viability for this class of compounds. As expected, compounds with aromatic methoxy substitution presented •CH3 radical elimination as the principal fragmentation pathway, forming dystonic ions. Compounds without methoxy substituents dissociate with higher energies losing the CO2, CO and H2O. The isotopic marking experiments indicated the exchange of hydrogens by deuterases in the hydroxyl protons, which corroborates with the proposed mechanisms.

Non-targeted and suspect analyses with liquid chromatography/electrospray/high-resolution mass spectrometry (LC/ESI/HRMS) are gaining importance as they enable identification of hundreds or even thousands of compounds in a single sample. Here, we present an approach to address the challenge to quantify compounds identified from LC/HRMS data without authentic standards. The approach uses random forest regression to predict the response of the compounds in ESI/HRMS with a mean error of 2.2 and 2.0 times for ESI positive and negative mode, respectively. We observe that the predicted responses can be transferred between different instruments via a regression approach. Furthermore, we applied the predicted responses to estimate the concentration of the compounds without the standard substances. The approach was validated by quantifying pesticides and mycotoxins in six different cereal samples. For applicability, the accuracy of the concentration prediction needs to be compatible with the effect (e.g. toxicology) predictions. We achieved the average quantification error of 5.4 times, which is well compatible with the accuracy of the toxicology predictions.

No analytical assay is currently available for the simultaneous determination of CBD major metabolites in serum or urine samples of individuals treated with medical cannabis or CBD-based pharmaceuticals. We developed and validated a method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for quantifying cannabidiol (CBD) and its metabolites, cannabidiol-7-oic acid (7-COOH-CBD), 7hydroxycannabidiol (7-OH-CBD), 6-alpha-hydroxycannabidiol (6-alpha-OH-CBD) and 6-beta-hydroxycannabidiol (6-beta-OH-CBD) in serum and urine samples of an individual treated with medical cannabis. The ionization was performed by electrospray in negative mode to reach the sensitivity required to detect trace amounts, with limits of quantification ranging from 0.05 to 0.1 ng/mL. The method is accurate (average inter/intra-day error

A widely applicable analytical LC/HRMS method based on ion source optimization, data treatment optimization on rice matrix was developed. The effects of key parameters of ion source, and their interactions on ESI response were studied on HPLC-QTOF. Compared with center points, 40% and 20% increase of response factors in the positive and negative mode can be achieved by ion source optimization, respectively. Data processing strategies inspired from metabolomics and multi-targeted analysis were compared and developed using case and control rice samples. Highly automated workflow using XCMS achieved highest mass accuracy, highest detection rate of 96% for 5 μg/kg in a non-targeted way. A clear distinction between the control and contaminated samples by PCA and PLS-DA was also achieved by this workflow using XCMS, even for the concentration of 5 μg/kg.

Brittle failure of key-hole notches is investigated experimentally and theoretically under mixed mode I/II loading with negative mode I contributions. The key-hole notched Brazilian disk specimen made of the general-purpose Polystyrene is utilized for conducting the fracture experiments. To predict the experimental results, the key-hole notch maximum tangential stress and key-hole notch mean stress criteria are utilized. It is shown that both criteria could provide good predictions to the experimental results of the fracture load. Moreover, the key-hole notch mean stress criterion with the experimentally determined critical distance is shown to be the most accurate failure criterion.

RATIONALE An application of microdialysis sampling for evaluation of the interaction property of small molecules to macromolecules is presented. Microdialysis combined with liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (LC/QTOF-MS/MS) was established for the purpose of screening of the multiple bioactive compounds in traditional Chinese medicines (TCMs). METHODS Microdialysis experiments were performed in vitro using a syringe pump and probes. Separation was achieved via liquid chromatography, and MS analysis was conducted by electrospray ionization quadrupole time-of-flight mass spectrometry in negative mode. The interaction property of compounds in TCMs with aldose reductase can be deduced from the comparison of the peak areas in chromatograms using a stable internal standard. RESULTS In this work, 23 compounds including iridoids, flavonoids, monoterpenoids, carotenoids and phenolic acids were identified by comparison with reference compounds, characteristic high-resolution mass spectrometry and the MS/MS fragmentations simultaneously. Binding degrees of 23 compounds in Gardenia jasminoides Eliis (G. jasminoide) with aldose reductase ranged from 13.91% to 66.25%. Also, microdialysis recoveries of 23 compounds in G. jasminoides were determined. CONCLUSIONS The Interaction properties of 23 compounds in G. jasminoides with aldose reductase were investigated and they are potential bioactive ingredients. Microdialysis coupled to LC/QTOF-MS/MS can be used for screening of bioactive multicomponents from TCMs with appropriate targets. Copyright © 2016 John Wiley & Sons, Ltd.

The well-known round-tip V-notched Brazilian disk specimen is utilized for conducting mixed mode I/II fracture tests on PMMA under negative mode I conditions for different notch angles and various notch radii with the aim to measure experimentally the fracture load and the fracture initiation angle. It is shown by the finite element analysis that although the notch is under negative mode I loading, one side of the notch border still experiences tensile tangential stresses suggesting that fracture would take place from the same side of notch border. Experimental observations also indicated that fracture occurs from the tensile side of the notch border confirming the finite element results. The experimental results are then theoretically estimated by means of two stress-based brittle fracture criteria, namely the round-tip V-notch maximum tangential stress and the mean-stress criteria. It is shown that both criteria provide very good predictions to the experimental results obtained under negative mode I conditions.

The complex mixture of dissolved organics in oil sands process-affected water (OSPW) is acutely lethal to fish at environmentally relevant concentrations, but few bioconcentration factors (BCFs) have been measured for its many chemical species. Japanese medaka (Oryzias latipes) were exposed to 10% OSPW, and measured BCFs were evaluated against predicted BCFs from octanol-water distribution ratios (DOW) and phospholipid membrane-water distribution ratios (DMW). Two heteroatomic chemical classes detected in positive ion mode (SO(+), NO(+)) and one in negative mode (O2(-), also known as naphthenic acids) had the greatest DMW values, as high as 10 000. Estimates of DMW were similar to and correlated with DOW for O(+), O2(+), SO(+), and NO(+) chemical species, but for O2(-) and SO2(-) species the DMW values were much greater than the corresponding DOW, suggesting the importance of electrostatic interactions for these ionizable organic acids. Only SO(+), NO(+), and O2(-) species were detectable in medaka exposed to OSPW, and BCFs for SO(+) and NO(+) species ranged from 0.6 to 28 L/kg, lower than predicted (i.e., 1.4-1.7 × 10(3) L/kg), possibly because of biotransformation of these hydrophobic substances. BCFs of O2(-) species ranged from 0.7 to 53 L/kg, similar to predicted values and indicating that phospholipid partitioning was an important bioconcentration mechanism.

Subsequent to Harper’s review essay centered on Brooke’s Climate Change and the Course of Global History: A Rough Journey, Brooke concedes that he could have focused more attention on the problem of the Malthusian trap. He stresses, nevertheless, that his reservations regarding the concept of Malthusian crises in pre-industrial societies are well placed, given the concept’s prominence in the large-scale environmental histories written during the past several decades. Turning to the impact of climate change in late classical antiquity, Brooke discusses established and new evidence for increasing, sometimes catastrophic, precipitation from the Mediterranean area into central Asia after a.d. 500 and after 1250, as a result of shifts toward the negative mode of the North Atlantic Oscillation. He also surveys the evidence for emerging arguments that this cooling-driven precipitation may have triggered outbreaks of bubonic plague in Central Asia.

In this study, a new method for simultaneous determination of cyantraniliprole, chlorantraniliprole, tetrachlorantraniliprole, cyclaniliprole and flubendiamide in edible mushrooms by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) combined with a modified QuEChERS procedure. The samples were extracted using acetonitrile and then cleaned up by primary secondary amine (PSA) and octadecylsilane (C18). The determination of these insecticides was achieved in less than 5 min using an electrospray ionization source in positive mode (ESI+) for cyantraniliprole and chlorantraniliprole, while negative mode (ESI−) for tetrachlorantraniliprole, cyclaniliprole and flubendiamide. The linearities of the calibrations for all target compounds were acceptable (R2 ≥ 0.9922). The limits of detection and quantification were 0.05–2 μg kg−1 and 5 μg kg−1, respectively. Acceptable recoveries (73.5–110.2%) were acquired for these insecticides with RSDs less than 12.7%. The results demonstrated that the proposed method was effective and convenient for the determination of these insecticides in edible mushrooms.

Secondary metabolites characterization of ethanol extracts of Palicourea sessilis leaves and stems by UPLC-DAD-ESI-MS/MS led to putative identification of hydrolysable tannins in leaf extract (ESI negative mode) while hydroxycinnamic acid amides (HCA) such as N-p-coumaroylputrescine and N-feruloylagmatine were detected in both leaf and stems extracts in the ESI positive mode. Secondary metabolites quantification data showed a higher content of total phenolic in the leaf extract while the total alkaloids contents are statistically equivalent in both of the extracts. Furthermore, monoterpene indole alkaloids were not detected in both extracts. The presence of HCA is here firstly reported for a Palicourea species. This finding increases the classes of secondary metabolites occurring in this genus.