Accurate Mass Measurements Research Articles

Design, Modelling, and Experimental Validation of a Glass U-Tube Mass Sensing Cantilever for Particulate Direct-on-Line Emissions Measurement

The requirement to monitor and control industrial processes has increased over recent years, therefore innovative techniques are required to meet the demand for alternative methods of particulate measurement. Resonant mass sensors are now strong candidates for accurate mass measurement and are frequently used in many diverse fields of science and engineering. This paper presents the design, modelling, and optimal geometry selection for sensitivity improvement of a U-shaped glass tube as a resonant mass sensing cantilever with a view to becoming a component of particulate measurement equipment. Finite Element Analysis (FEA) was used to develop the system which was validated experimentally using a physical model. This paper focuses on both the proof of concept and the geometry selection of the sensor using analysis of the system sensitivity for best selection. Modal and harmonic analysis were undertaken across a range of commercially available glass tube sizes from 6 mm to 10 mm diameter, to determine the optimal geometry selection, validated with practical experimental data. Results show a consistent difference of 3–5% between the simulation and experimental results, showing strong correlation. This research provides a methodology on the development of using a U-shaped glass tube for accurate mass measurement with a view to exploring the design as a component of particulate emissions equipment. The experimental and simulation results confirm that the highest sensitivity is achieved when the geometry dimensions, and therefore the vacant mass of the tube, is reduced. The 6 mm diameter tube with the smallest bend radius was the most suitable design to meet the design criteria. The calibration curve was plotted to allow an unknown mass to be calculated, which gave an R2 value of 0.9984. All experimental work was repeated three times with results giving an average of 0.44% between the minimum and maximum showing strong linearity and suggesting the potential for implementation of the methodology in its intended application. The design provides possible solutions to some of the issues currently seen with particulate measurement from stationary sources.

Target and untargeted screening of perfluoroalkyl substances in biota using liquid chromatography coupled to quadrupole time of flight mass spectrometry

Perfluoroalkyl substances (PFAS) are known to bioaccumulate and trigger adverse effects in marine birds. This study develops an extraction and analytical methodology for the target/untargeted analysis of PFAS in eggs of Yellow-legged gull (Larus michahellis) and Audouin's gull (Larus audouinii) and blood of Greater flamingo (Phoenicopterus roseus), which are used as bioindicators of organic chemical pollution. Samples were extracted by ultrasonication with acetonitrile and cleaned-up with activated carbon, and analysis was performed by ultra-high-performance liquid chromatography coupled to a quadrupole-time of flight mass spectrometer (UHPLC-Q-TOF) with negative electrospray ionization. Data-independent acquisition (DIA) was performed through full-scan acquisition to obtain MS1 at 6 eV and MS2 at 30 eV. In a first step, quantitative analysis of 25 PFAS was performed using 9 mass-labelled internal standard PFAS and quality parameters of the method developed are provided. Then, an untargeted screening workflow is proposed using the high-resolution PFAS library database from NORMAN to identify new chemicals through accurate mass measurement of MS1 and MS2 signals. The method permitted to detect several PFAS at concentrations ranging from 0.45 to 55.2 ng/g wet weight in gull eggs and from 0.75 to 125 ng/mL wet weight in flamingos’ blood, with PFOS, PFOA, PFNA, PFUdA, PFTrDA, PFDoA, PFHxS and PFHpA the main compounds detected. In addition, perfluoro-p-ethylcyclohexylsulfonic acid (PFECHS, CAS number 646-83-3) and 2-(perfluorohexyl)ethanol (6:2 FTOH, CAS number 647-42-7) were tentatively identified. The developed UHPLC-Q-TOF target/untargeted analytical approach increases the scope of PFAS analysis, enabling a better assessment on contaminant exposure and promoting the use of bird species as bioindicators of chemical pollution.

Volatility Measurements of Individual Components in Organic Aerosol Mixtures Using Temperature-Programmed Desorption-Direct Analysis in Real Time-High Resolution Mass Spectrometry.

Atmospheric organic aerosols (OA) have profound effects on air quality, visibility, and radiative forcing of climate. Quantitative assessment of gas-particle equilibrium of OA components is critical to understand formation, growth, distribution, and evolution of OA in the atmosphere. This study presents a novel ambient pressure measurement approach developed and tested for untargeted screening of individual components in complex OA mixtures, followed by targeted chemical speciation of identified species and assessment of their physicochemical properties such as saturation vapor pressure and enthalpies of sublimation/evaporation. The method employs temperature-programmed desorption (TPD) experiments coupled to "direct analysis in real time" (DART) ionization source and high resolution mass spectrometry (HRMS) detection. Progression of the mass spectra is acquired in the TPD experiments over a T = 25-350 °C temperature range, and extracted ion chromatograms (EIC) of individual species are used to infer their apparent enthalpies of sublimation/evaporation (ΔHsub*) and saturation vapor pressure (pT*, Pa, or CT*, μg m-3) as a function of T. We validate application of this method for analysis of selected organic compounds with known ΔHsub and CT values, which showed excellent agreement between our results and the existing data. We then extend these experiments to interrogate individual components in complex OA samples generated in the laboratory-controlled ozonolysis of α-pinene, limonene, and β-ocimene monoterpenes. The abundant OA species of interest are distinguished based on their accurate mass measurements, followed by quantitation of their apparent ΔHsub* and CT* values from the corresponding EIC records. Comparison of C298K* values derived from our experiments for the individual OA components with the corresponding estimates based on their elemental composition using a "molecular corridors" (MC) parametrization suggests that the MC calculations tend to overestimate the saturation vapor pressures of OA components. Presented results indicate very promising applicability of the TPD-DART-HRMS method for the untargeted analysis of organic molecules in OA and other environmental mixtures, enabling rapid detection and quantification of organic pollutants in the real-world condensed-phase samples at atmospheric pressure and without sample preparation.

Achieving Sub-Parts-per-Million Mass Measurement Accuracy on an Orbitrap Mass Spectrometry Imaging Platform without Automatic Gain Control

The collection of profile data is standard practice within the field of mass spectrometry (MS). However, profile data collection often results in large data files that require extensive processing times, especially in mass spectrometry imaging (MSI) studies where thousands of high-resolution scans are recorded. Natively collecting centroid MS data is an alternative that effectively reduces both the resulting file size and the data processing time. Herein, high-resolution accurate mass (HRAM) Orbitrap MSI data on mouse liver tissue sections without automatic gain control (AGC) were natively collected in both profile and centroid modes and compared based on the file size and processing time. Additionally, centroid data were evaluated against the profile data with regard to the spectra integrity, mass measurement accuracy (MMA), and the number of lipid annotations to ensure that centroid data did not compromise the data quality. For both native and postacquisition centroided data, the variation in mass measurement accuracy decreased relative to the profile data collection. Furthermore, centroid data collection increased the number of METASPACE database annotations indicating higher sensitivity and greater accuracy for lipid annotation compared to native profile data collection. Profile MSI data was shown to have a higher likelihood of false positive identifications due to an increased number of data points on either side of the peaks, whereas the same trend was not observed in data collected in native centroid data collection. This publication explores and explains the importance in properly centroiding MSI data, either natively or by adequate centroiding methods, to obtain the most accurate information and come to the best conclusions. These data support that natively collecting centroid data significantly improves MMA to sub-ppm levels without AGC and reduces false positive annotations.

Wearable Resonator-Based Respirable Dust Monitor for Underground Coal Mines

Exposure to respirable coal dust and diesel exhaust in underground coal mines can cause detrimental airway diseases such as coal worker’s pneumoconiosis (CWP), silicosis, and lung cancer. In this article, we present the design, fabrication, and experimental evaluation of a low-cost wearable respirable dust monitor (WEARDM) that uses a dual-resonator gravimetric sensing approach for real-time measurement of respirable airborne particulate matter (PM) concentrations. The sensor selects for the ISO-respirable dust fraction using a miniature virtual impactor (VI) and removes moisture from the collected dust to ensure accurate mass measurement. WEARDM uses a novel dual-resonator mass sensor (DRMS) that is composed of a quartz crystal microbalance (QCM) and a film bulk acoustic resonator (FBAR). The QCM measures the mass concentration of particles generated from coal mining operations [typically >2.5- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> aerodynamic diameter (AD)], separated using inertial impaction. Thermophoretic precipitation is used to deposit the fine and ultrafine particles, such as those emitted from diesel sources [typically <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$ &lt; 0.1~\mu \text{m}$ </tex-math></inline-formula> AD) on FBAR. This allows the WEARDM system to maintain a large dynamic range and uniform collection efficiency (CE) across the entire respirable fraction. The WEARDM system is optimized for a low flow rate of 250 mL/min which results in low power usage and a small form factor and is an order of magnitude smaller and less expensive than currently available devices.

Accurate Determination of Pesticide Residues in Milk by Sonication-QuEChERS Extraction and LC-LTQ/Orbitrap Mass Spectrometry

A modified, quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction procedure combined with sonication and Ultra-High Performance Liquid Chromatography–Orbitrap-Mass Spectrometry (UHPLC–Orbitrap-MS) was developed as a sensitive and reliable methodology for the determination of multiclass pesticides in full-fat milk. Different amounts of EMR-lipid sorbent were assayed for the cleanup step in order to achieve both acceptably high recoveries and low co-extractives in the final extracts. Accurate mass measurements of the analyte’s pseudo-molecular ions and tandem MS fragmentation were used to quantify and identify the target pesticides. Analytical performance characteristics of the method, such as linearity, recovery, precision, the limit of detection (LOD) and quantification (LOQ), matrix effects (ME), and expanded uncertainty, have been determined for method validation fulfilling all criteria for its use as a validated routine method. The method was successfully applied to real samples (by local farms and commercial), revealing the presence of carbendazim in one milk sample at a concentration level below the maximum residue limits.

Automated method using direct-immersion solid-phase microextraction and on-fiber derivatization coupled with comprehensive two-dimensional gas chromatography high-resolution mass spectrometry for profiling naphthenic acids in produced water

Naphthenic acids (NAs) are naturally occurring organic acids in petroleum and are found in waste waters generated during oil production (produced water, PW). Profiling this class of compounds is important due to flow assurance during oil exploration. Compositional analysis of PW is also relevant for waste treatment to reduce negative impacts on the environment. Here, comprehensive two-dimensional gas chromatography coupled with high-resolution mass spectrometry (GC×GC–HRMS) was applied as an ideal platform for qualitative analysis of NAs by combining the high peak capacity of the composite system with automated scripts for group-type identification based on accurate mass measurements and fragmentation patterns. To achieve high-throughput profiling of NAs in PW samples, direct-immersion solid phase microextraction (DI-SPME) was selected for extraction, derivatization and preconcentration. A fully automated DI-SPME method was developed to combine extraction, fiber rinsing and drying, and on-fiber derivatization with N-methyl-N‑tert-butyldimethylsilyltrifluoroacetamide (MTBSTFA). Data processing was based on filtering scripts using the Computer Language for Identifying Chemicals (CLIC). The method successfully identified up to 94 NAs comprising carbon numbers between 6 and 18 and hydrogen deficiency values ranging from 0 to -4. The proposed method demonstrated wider extraction coverage compared to traditional liquid-liquid extraction (LLE) – a critical factor for petroleomic investigations. The method developed also enabled quantitative analysis, exhibiting detection limits of 0.5 ng L−1 and relative standard deviation (RSD) at a concentration of NAs of 30 µg L−1 ranging from 4.5 to 25.0%.

X-ray analysis of JWST’s first galaxy cluster lens SMACS J0723.3−7327

Context. SMACS J0723.3−7327 is the first galaxy cluster lens observed by James Webb Space Telescope (JWST). Based on its early release observation data, several groups have reported the results on strong lensing analysis and mass distribution of this cluster. The new lens model dramatically improves upon previous results, thanks to JWST’s unprecedented sensitivity and angular resolution. However, limited by the angular coverage of the JWST data, the strong lensing models only cover the central region. Conducting an X-ray analysis on the hot intracluster medium (ICM) is necessary to obtain a more complete constraint on the mass distribution in this very massive cluster. Aims. In this work, we perform a comprehensive X-ray analysis of J0723 with an aim to obtain accurate ICM hydrostatic mass measurements, using the X-ray data from Spectrum Roentgen Gamma (SRG)/eROSITA and Chandra X-ray observatories. By comparing the hydrostatic mass profile with the strong lensing model, we aim to provide the most reliable constraint on the distribution of mass up to R500. Methods. Thanks to the eROSITA all-sky survey and Chandra, which provide high signal-to-noise ratio (S/N) and high angular resolution data, respectively, we were able to constrain the ICM gas density profile and temperature profile with good accuracy both in the core and to the outskirts. With the density and temperature profiles, we computed the hydrostatic mass profile, which was then projected along the line of sight to compare with the mass distribution obtained from the recent strong lensing analysis based on JWST data. We also deprojected the strong lensing mass distribution using the hydrostatic mass profile obtained in this work. Results. The X-ray results obtained from eROSITA and Chandra are in very good agreement. The hydrostatic mass profiles we measured in this work, both projected and deprojected, are in good agreement with recent strong lensing results based on JWST data, at all radii. The projected hydrostatic mass within 128 kpc (the estimated Einstein radius) is (8.0 ± 0.7)×1013 M⊙, consistent with the strong lensing mass reported in recent literature. With the hydrostatic mass profile, we measured R2500 = 0.54 ± 0.04 Mpc and M2500 = (3.5 ± 0.8)×1014 M⊙, while the R500 and M500 are 1.32 ± 0.23 Mpc and (9.8 ± 5.1)×1014 M⊙, with a relatively larger error bar due to the rapidly decreasing S/N in the outskirts. We also find that the radial acceleration relation in J0723 is inconsistent with the RAR for spiral galaxies, implying that the latter is not a universal property of gravity across all mass scales.

Analysis of Isotopically Depleted Proteins Derived from Escherichia coli and Caenorhabditis elegans Cell Lines by Liquid Chromatography 21 T Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry.

Protein mass measurement by mass spectrometry is complicated by wide isotopic distributions that result from incorporation of heavy isotopes of C, H, N, O, and S, thereby limiting signal-to-noise ratio (SNR) and accurate intact mass determination, particularly for larger proteins [Fenselau et al. Anal. Chem. 1983, 55 (2), 353-356]. Observation of the monoisotopic mass-to-charge ratio (m/z) is the simplest and most accurate way to determine intact protein mass, but as mass increases, the relative abundance of the monoisotopic peak becomes so low that it is often undetectable. Here, we used an isotopically depleted growth medium to culture bacterial cells (Escherichia coli), resulting in isotopically depleted proteins. Isotopically depleted proteins show increased sequence coverage, mass measurement accuracy, and increased S/N of the monoisotopic peak by Fourier transform ion cyclotron resonance mass spectrometry analysis. We then grew Caenorhabditis elegans cells in a medium containing living isotopically depleted E. coli cells, thereby producing the first isotopically depleted eukaryotic proteins. This is the first time isotopic depletion has been implemented for four isotopes (1H, 12C, 14N, and 16O), resulting in the highest degree of depletion ever used for protein analysis and further improving MS analysis.

Differentiation between Isomeric 4,5-Functionalized 1,2,3-Thiadiazoles and 1,2,3-Triazoles by ESI-HRMS and IR Ion Spectroscopy.

A large variety of 1,2,3-thiadiazoles and 1,2,3-triazoles are used extensively in modern pure and applied organic chemistry as important structural blocks of numerous valuable products. Creation of new methods of synthesis of these isomeric compounds requires the development of reliable analytical tools to reveal the structural characteristics of these novel compounds, which are able to distinguish between isomers. Mass spectrometry (MS) is a clear choice for this task due to its selectivity, sensitivity, informational capacity, and reliability. Here, the application of electrospray ionization (ESI) with ion detection in positive and negative modes was demonstrated to be useful in structural studies. Additionally, interconversion of isomeric 4,5-functionalized 1,2,3-triazoles and 1,2,3-thiadiazoles was demonstrated. Application of accurate mass measurements and tandem mass spectrometry in MS2 and MS3 modes indicated the occurrence of gas-phase rearrangement of 1,2,3-triazoles into 1,2,3-thiadiazoles under (+)ESI-MS/MS conditions, independent of the nature of substituents, in line with the reaction in the condensed phase. Infrared multiple photon dissociation (IRMPD) spectroscopy enabled the establishment of structures of some of the most crucial common fragment ions, including [M+H-N2]+ and [M+H-N2-RSO2]+ species. The (-)ESI-MS/MS experiments were significantly more informative for the sulfonyl alkyl derivatives compared to the sulfonyl aryl ones. However, there was insufficient evidence to confirm the solution-phase transformation of 1,2,3-thiadiazoles into the corresponding 1,2,3-triazoles.

193 nm Ultraviolet Photodissociation for the Characterization of Singly Charged Proteoforms Generated by MALDI.

MALDI imaging allows for the near-cellular profiling of proteoforms directly from microbial, plant, and mammalian samples. Despite detecting hundreds of proteoforms, identification of unknowns with only intact mass information remains a distinct challenge, even with high mass resolving power and mass accuracy. To this end, many supplementary methods have been used to create experimental databases for accurate mass matching, including bulk or spatially resolved bottom-up and/or top-down proteomics. Herein, we describe the application of 193 nm ultraviolet photodissociation (UVPD) for fragmentation of quadrupole isolated singly charged ubiquitin (m/z 8565) by MALDI-UVPD on a UHMR HF Orbitrap. This platform permitted the high-resolution accurate mass measurement of not just terminal fragments but also large internal fragments. The outlined workflow demonstrates the feasibility of top-down analyses of isolated MALDI protein ions and the potential toward more comprehensive characterization of proteoforms in MALDI imaging applications.

Hydroxyl transfer versus cyclization reaction in the gas phase: Sequential loss of NH3 and CH2CO from protonated phenylalanine derivatives.

Collisional activation of protonated phenylalanine derivatives deamination products leads to hydroxyl skeletal rearrangement versus cyclization reaction, and to form hydroxylbenzyl cation via elimination of CH2CO. To better clarify this unusual fragmentation reaction, accurate mass measurements experiments, native isotope experiments, multiple-stage mass spectrometry experiments, different substituents experiments, and density functional theory (DFT) calculations were carried out to investigate the dissociation mechanistic pathways of protonated phenylalanine derivatives deamination products. In route 1, a three-membered ring-opening reaction and a 1,3-hydroxyl transfer (from the carbonyl carbon atom to the interposition carbon atom of carbonyl) occurs to form 3-hydroxy-1-oxo-3-phenylpropan-1-ylium, followed by dissociation to lose CH2CO to give hydroxy (phenyl)methylium. In route 2, a successive cyclization rearrangement reaction and proton transfer occur to form a 2-hydroxylphenylpropionyl cation or protonated 2-hydroxy-4H-benzopyran, followed by dissociation to lose CH2CO or CH≡COH to give 2-hydroxylbenzyl cation. In route 3, a successive hydroxyl transfer (from the carbonyl carbon atom to the ortho carbon atom on benzene) and two stepwise proton transfer (1,2-proton transfer to the ipso-carbon atom of the phenyl ring followed by 1,3-proton transfer to the ortho carbon atom of carbonyl) occurs to form a 2-hydroxylphenylpropionyl cation, which subsequently dissociates to form 2-hydroxylbenzyl cation by elimination of CH2CO. DFT calculations suggested that route 1 was more favorable than route 2 and route 3 from a thermodynamic point of view.

Research on the Pose Error Compensation Technology for the Mass and Centroid Measurement of Large-Sized Aircraft Based on Kinematics

The accurate measurement of mass and centroid is indispensable for accurate control of aircraft. In order to eliminate the influence of assembly error and product pose error on the measurement results, a multi-station measurement idea that can self-compensate for the geometric parameter error is proposed in this paper based on. At the same time, the kinematic model of the mechanical structure of the measurement equipment is established to prove the effectiveness of the structure in error compensation theoretically, and the experimental verification of the standard part and aircraft is carried out. The test results show that the measurement results using the idea of the multi-station compensation measurement are significantly better than those of the more common methods, with the mass measurement accuracy of 0.03% and the centroid error within ±0.15 mm, meeting the requirement of high precision measurement for the mass properties.

Tailoring the Sensitivity of Microcantilevers To Monitor the Mass of Single Adherent Living Cells.

Microcantilevers are widely employed as mass sensors for biological samples, from single molecules to single cells. However, the accurate mass quantification of living adherent cells is impaired by the microcantilever's mass sensitivity and cell migration, both of which can lead to detect masses mismatching by ≫50%. Here, we design photothermally actuated microcantilevers to optimize the accuracy of cell mass measurements. By reducing the inertial mass of the microcantilever using a focused ion beam, we considerably increase its mass sensitivity, which is validated by finite element analysis and experimentally by gelatin microbeads. The improved microcantilevers allow us to instantly monitor at much improved accuracy the mass of both living HeLa cells and mouse fibroblasts adhering to different substrates. Finally, we show that the improved cantilever design favorably restricts cell migration and thus reduces the large measurement errors associated with this effect.

Mass calibrants for positive chemical ionization-high resolution mass spectrometry (CI-HRMS) for the identification of unknown compounds using accurate mass measurements.

Gas Chromatography-Electron Ionization-Mass Spectrometry (GC-EI-MS) is still the most routinely performed method for metabolite profiling as compared to other hyphenated techniques. But when it comes to identification of unknown compounds, information on the molecular weight is not readily available because the molecular ion is not always found with electron ionization (EI). Thus, the use of chemical ionization (CI) is envisaged that commonly produces the molecular ion; in combination with accurate mass measurement, this technique would further allow for calculation of sum formulas of those compounds. However, for proper accuracy of analysis, a mass calibrant is needed. We set out to find a commercially available reference material with mass peaks that would qualify the substance as mass calibrant under CI conditions. Six commercially available mass calibrants, FC 43, PFK, Ultramark 1621, Ultramark 3200F, Triton X-100, and PEG 1000, were tested under CI conditions to understand their fragmentation behavior. Our findings indicate that Ultramark 1621 and PFK best fit the expectations of a mass calibrant for HRMS analysis whereby PFK provided a fragmentation pattern similar to EI outcomes thus enabling the use of mass reference tables commonly provided within commercial mass spectrometers. On the other hand, Ultramark 1621 is a mixture of fluorinated phosphazines that shows stable fragment intensities.

Hygroscopic growth of single atmospheric sea salt aerosol particles from mass measurement in an optical trap.

Sea salt aerosol is among the most abundant aerosol species in Earth's atmosphere, and its hygroscopicity is an important parameter to quantify its interaction with solar radiation. Conflicting values for the hygroscopic growth have been reported in the literature, which decreases the accuracy with which their impact on Earth's climate can be modelled. Here we report new values of the hygroscopic growth for a selection of salt compositions representative of atmospheric sea salt. These values are obtained from single optically trapped aqueous droplets with dry radii between 0.3 and 2 μm, using a recently developed method for single particle mass measurement in an optical trap. We compare our results to earlier studies and propose a way to reconcile the apparent discrepancies found in the literature. Within our studies, we also observe the crystallization of CaSO4·2H2O (Gypsum) during the drying of optically trapped sea salt droplets at significantly larger relative humidity of 65-68% than the main efflorescence relative humidity at 50%. This preceding transition occurred in the absence of any contact of the particle with a surface.

Measuring the Dust Masses of Protoplanetary Disks in Lupus with ALMA: Evidence That Disks Can Be Optically Thick at 3 mm

Accurate disk mass measurements are necessary to constrain disk evolution and the timescale of planet formation, but such measurements are difficult to make and are very dependent on assumptions. Here, we look at the assumption that the disk is optically thin at radio wavelengths and the effect of this assumption on measurements of disk dust mass. We model the optical to radio spectral energy distributions of 41 protoplanetary disks located in the young (∼1–3 Myr old) Lupus star-forming region, including 0.89 1.33 and 3 mm flux densities when available. We measure disk dust masses that are ∼1.5–6 times higher than when using the commonly adopted disk dust mass equation under the assumption of optically thin emission in the (sub)millimeter range. The cause of this discrepancy is that most disks are optically thick at millimeter wavelengths, even up to 3 mm, demonstrating that observations at longer wavelengths are needed to trace the fully optically thin emission of disks.

Identification and characterization of the metabolites of moscatilin in mouse, rat, dog, monkey and human hepatocytes by LC-Orbitrap-MS/MS combined with diagnostic fragment ions and accurate mass measurements.

Moscatilin, a bibenzyl derivative from the stem of Dendrobium loddigesii, has been shown to have anticancer activity. The aim of this study was to identify and characterize the possible in vitro metabolites of moscatilin generated from hepatocytes. The metabolites generated in the hepatocytes of mouse, rat, dog, monkey and human were identified and characterized employing ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap tandem mass spectrometry (LC-Orbitrap-MS/MS) based on diagnostic fragment ions and accurate mass measurements. A total of 18 metabolites were identified, among which seven were phase I and 11 were phase II metabolites. The plausible structures of the metabolites and the probable biotransformation pathways were proposed based on the diagnostic fragment ions, chemical formula and mass fragmentation pattern, as well as the accurate masses. The majority of phase I metabolites were generated by demethylation and hydroxylation, while phase II metabolites were mainly generated by glucuronidation, glutathione conjugation and sulfation. Our study first expounded the metabolites of moscatilin in mouse, rat, dog, monkey and human hepatocytes and provided a foundation for a further pharmacokinetic and toxicity study. More importantly, LC-Orbitrap-MS/MS combined with diagnostic fragment ions and accurate mass measurements has been proved to be an effective method for the rapid identification of bibenzyl derivatives and their metabolites.

Characterization and identification of chemical constituents in Corni Fructus and effect of storage using UHPLC-LTQ-Orbitrap-MS

Corni Fructus (CF) has been widely used as both traditional medicine and food; however, systematic studies on its chemical profile and the impact of storage periods on the indicative components are lacking. In this study, UHPLC-LTQ-Orbitrap-MS was used to investigate the fragmentation behaviors of multiple compounds from CF and the content variety of its indicative components for different storage periods. The major basic components of CF were determined to be iridoid glucosides, pentacyclic triterpenoids, phenolic acids, tannins and flavonoids. The characteristic cleavage pathways of the iridoid glucosides, pentacyclic triterpenoids, phenolic acids, tannins and flavonoids were further investigated and elaborated, which could assist in identifying the structures of similar components of other Chinese herbal medicines. Using accurate mass measurements for each precursor ion and the subsequent fragmented ions, and then comparing with standards and literature data, a total of 130 components, including 69 iridoid glucosides, 9 pentacyclic triterpenoids, 16 phenolic acids, 20 tannins and 16 flavonoids, 47 of which are potentially new compounds, were identified. The storage period studies indicated that the contents of 19 indicative components in CF changed differently with the prolongation of the storage period. Among them, morroniside, loganin, sweroside, cornuside, gallic acid, oleanolic acid and ursolic acid were the most important. These results provide abundant information for the identification and improved understanding of the chemical constituents in CF to clarify the content variety of its indicative components for different storage periods.

Combined strong and weak gravitational lensing mass measurements in clusters of galaxies

AbstractGravitational lensing in clusters of galaxies is one of the most powerful methods to probe the dark matter mass distribution inside such systems, after mapping the baryonic component, and test the currently accepted ɅCDM cosmological paradigm. With the advent of new high-resolution facilities such as the JWST, strong lensing (SL) is capable of providing extremely accurate mass measurements in the densest regions of such structures. Weak lensing (WL) provides complementary information by measuring the total mass distribution in the outskirts of galaxy clusters, where no multiple images of background sources are produced.In my talk, I will present updates on the WL mass reconstruction of the Frontier Fields galaxy cluster Abell 2744 (z = 0.308) based on Subaru, Magellan, and JWST data, and I will show how the results obtained, combined with accurate SL modeling of this lens, provide a consistent picture of the cluster total mass distribution. I will discuss the pipeline used for this work, the extensive checks performed on the different datasets and the scientific results obtained. Being composed of several substructures undergoing a merging process, the complex geometry of this cluster makes it an ideal laboratory to verify the consistency and reliability of the results obtained with the two methods. I will compare the predictions of the SL models extrapolated in the outer regions of the cluster with the non-parametric WL mass reconstruction to look for potential systematic effects affecting the SL analysis.