Accurate Mass Measurements Research Articles

General Mass Property Measurement Equipment for Large-Sized Aircraft.

The accurate measurement of aircraft mass properties, such as the mass, centroid, and moment of inertia (MOI), plays a key role in the precise control of aircraft. In order to obtain high-precision information on the parameters of the mass, centroid, and MOI of an aircraft using a single instrument, an integrated mass property measurement system was developed in this study by analyzing and comparing the latest technologies, especially the function-switching device, which switches the measurement states between the center of mass and the MOI. The purpose of mass property measurement was achieved through single clamping. In addition, the system has strong versatility and expansion and can be used with different tooling or adapter rings to measure the mass properties of aircraft with different shapes. In this paper, the main mechanical structure of the measurement system, the measurement method of relevant mass parameters, and the solution method of the transformation matrix are introduced, and the standard parts and the aircraft were verified experimentally. The test results showed that the mass measurement accuracy was 0.03%, the centroid measurement error was within ±0.2 mm, and the measurement accuracy of the MOI was within 0.2%, all of which meet the high-precision measurement requirements for the mass properties.

Per- and polyfluoroalkyl substances (PFAS) determination in shellfish by liquid chromatography coupled to accurate mass spectrometry.

Data available on request due to privacy/ethical restrictions. Table S1. Analytes and associated isotope analogues used as surrogate and injection standards respectively Table S2. LC gradient Table S3. Compounds, RT, formula and accurate masses of the analysed compounds Table S4. PFAS candidates after suspect screening approach using accurate mass measurement (LC-QTOF) Table S5. Detection frequency and confidence level of the PFASs retrieved by suspect screening approach using accurate mass measurement (LC-QTOF) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Photometric Redshifts and Galaxy Clusters for DES DR2, DESI DR9, and HSC-SSP PDR3 Data

Photometric redshift (photoz) is a fundamental parameter for multi-wavelength photometric surveys, while galaxy clusters are important cosmological probes and ideal objects for exploring the dense environmental impact on galaxy evolution. We extend our previous work on estimating photoz and detecting galaxy clusters to the latest data releases of the Dark Energy Spectroscopic Instrument (DESI) imaging surveys, Dark Energy Survey (DES) and Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) imaging surveys and make corresponding catalogs publicly available for more extensive scientific applications. The photoz catalogs include accurate measurements of photoz and stellar mass for about 320, 293 and 134 million galaxies with r < 23, i < 24 and i < 25 in DESI DR9, DES DR2 and HSC-SSP PDR3 data, respectively. The photoz accuracy is about 0.017, 0.024 and 0.029 and the general redshift coverage is z < 1, z < 1.2 and z < 1.6, respectively for those three surveys. The uncertainty of the logarithmic stellar mass that is inferred from stellar population synthesis fitting is about 0.2 dex. With the above photoz catalogs, galaxy clusters are detected using a fast cluster-finding algorithm. A total of 532,810, 86,963 and 36,566 galaxy clusters with the number of members larger than 10 is discovered for DESI, DES and HSC-SSP, respectively. Their photoz accuracy is at the level of 0.01. The total mass of our clusters is also estimated by using the calibration relations between the optical richness and the mass measurement from X-ray and radio observations. The photoz and cluster catalogs are available at ScienceDB (https://www.doi.org/10.11922/sciencedb.o00069.00003) and PaperData Repository (https://doi.org/10.12149/101089).

On the Connection between Supermassive Black Holes and Galaxy Growth in the Reionization Epoch

The correlation between the mass of supermassive black holes (SMBHs; ) and their host galaxies () in the reionization epoch provides valuable constraints on their early growth. High-redshift quasars typically have an / ratio significantly elevated in comparison to the local value. However, the degree to which this apparent offset is driven by observational biases is unclear for the most distant quasars. To address this issue, we model the sample selection and measurement biases for a compilation of 20 quasars at z ∼ 6 with host properties based on ALMA observations. We find that the observed distribution of quasars in the plane can be reproduced by assuming that the underlying SMBH population at z ∼ 6 follows the relationship in the local universe. However, a positive or even a negative evolution in / can also explain the data, depending on whether the intrinsic scatter evolves and on the strength of various systematic uncertainties. To break these degeneracies, an improvement in the accuracy of mass measurements and an expansion of the current sample to lower limits are needed. Furthermore, assuming a radiative efficiency of 0.1 and quasar duty cycles estimated from the active SMBH fraction, significant outliers in / tend to move toward the local relation given their instantaneous BH growth rate and star formation rate. This may provide evidence for a self-regulated SMBH–galaxy coevolution scenario that is in place at z ∼ 6, with active galactic nucleus feedback being a possible driver.

A3COSMOS: A census on the molecular gas mass and extent of main-sequence galaxies across cosmic time

Aims. We aim to constrain for the first time the mean mass and extent of the molecular gas of a mass-complete sample of normal &gt; 1010 M⊙ star-forming galaxies at 0.4 &lt; z &lt; 3.6. Methods. We apply an innovative uv-based stacking analysis to a large set of archival Atacama Large Millimeter/submillimeter Array (ALMA) observations using a mass-complete sample of main-sequence (MS) galaxies. This stacking analysis, performed on the Rayleigh-Jeans dust continuum emission, provides accurate measurements of the mean mass and extent of the molecular gas of galaxy populations, which are otherwise individually undetected. Results. The molecular gas mass of MS galaxies evolves with redshift and stellar mass. At all stellar masses, the molecular gas fraction decreases by a factor of ∼24 from z ∼ 3.2 to z ∼ 0. At a given redshift, the molecular gas fraction of MS galaxies decreases with stellar mass at roughly the same rate that their specific star-formation rate (SFR/M⋆) decreases. The molecular gas depletion time of MS galaxies remains roughly constant at z &gt; 0.5 with a value of 300–500 Myr, but increases by a factor of ∼3 from z ∼ 0.5 to z ∼ 0. This evolution of the molecular gas depletion time of MS galaxies can be predicted from the evolution of their molecular gas surface density and a seemingly universal MS-only ΣMmol − ΣSFR relation with an inferred slope of ∼1.13, the so-called Kennicutt–Schmidt (KS) relation. The far-infrared size of MS galaxies shows no significant evolution with redshift or stellar mass, with a mean circularized half-light radius of ∼2.2 kpc. Finally, our mean molecular gas masses are generally lower than previous estimates, likely due to the fact that literature studies were largely biased toward individually detected MS galaxies with massive gas reservoirs. Conclusions. To first order, the molecular gas content of MS galaxies regulates their star formation across cosmic time, while variation in their star-formation efficiency plays a secondary role. Despite a large evolution of their gas content and star-formation rates, MS galaxies have evolved along a seemingly universal MS-only KS relation.

Electron ionization mass spectrometric fragmentation and multiple reaction monitoring quantification of ferulic and p-coumaric acid trimethylsilyl derivatives in deposited atmospheric particles.

Ferulic and p-coumaric acids are important biological and structural components of plant cell walls and possess antioxidant and antimicrobial properties. These phenolic acids are widespread in environmental samples. However, when they are present at very low concentrations or in very complex lipid extracts, their identification and quantification can be challenging. The electron ionization mass spectrometry (EI-MS) fragmentation pathways of ferulic and p-coumaric acid trimethylsilyl (TMS) derivatives were investigated. These pathways were deduced by (i) low-energy collision-induced dissociation (CID) gas chromatography (GC)/EI-MS/MS, (ii) accurate mass measurement, and (iii) 13 C labelling. These compounds were then characterized and quantified in multiple reaction monitoring (MRM) mode in total lipid extracts of deposited atmospheric particles using highly specific transitions based on the main fragmentation pathways elucidated. Low-energy CID-MS/MS analyses, accurate mass measurement and 13 C labelling enabled us to elucidate EI-MS fragmentations of ferulic and p-coumaric acid TMS derivatives. Some specific fragmentations proved useful for subsequent characterization and quantification of these compounds. As an application of some of the described fragmentations, trace amounts of these phenolic acids were characterized and quantified in MRM mode in wet- and dry-deposited atmospheric particles containing low proportions of organic matter. EI-MS fragmentations of ferulic and p-coumaric acid TMS derivatives exhibit specific fragment ions that can be very useful for the quantification of trace amounts of both phenolic acids in environmental samples.

Identification and characterization of higenamine metabolites in human urine by quadrupole-orbitrap LC-MS/MS for doping control

Higenamine is an alkaloid found in aconite, Annona squamosa, nanzhu (sacred bamboo), and other plants. It can be used to treat coughing, asthma, heart failure, and erectile dysfunction as well as aid in weight loss. It is also a banned substance in and out of competition as defined by the World Anti-Doping Agency (WADA). In this work, higenamine metabolic profiles were investigated in detail. Two healthy volunteers (one male and one female) took a higenamine tablet (5 mg), and urine samples were collected for two weeks. Solid-phase extraction (SPE) without enzymatic hydrolysis was used to clean the urine samples, and the urine extracts were then analyzed by liquid chromatography–quadrupole-orbitrap mass spectrometry (quadrupole-orbitrap LC–MS/MS) with accurate mass measurements. Higenamine and 32 metabolites were detected: 6 methylated, 10 sulfated and 16 glucuronidated metabolites. The chemical structures were elucidated by their fragmentation patterns, and accurate molecular formula determination was obtained for these newly reported metabolites. Three metabolic pathways containing methylation, glucuronidation, sulfation, and combinations of these were provided with methylation as the main metabolic pathway. The post-dose detection windows within urine of all 32 metabolites were compared with that of the parent drug, and a new potential biomarker (M7) was suggested for higenamine misuse. All urine samples were processed by two sample preparation methods: the dilute-and-shoot (DS) procedure and acid hydrolysis followed by SPE, and the time periods for a higenamine positive trails of two methods were compared. Although the DS method used to process the urine samples of athletes in the most of WADA-accredited laboratories to detect only free higenamine, acid hydrolysis followed by SPE is preferable and offers routine analysis to avoid false-negative results.

A new coupling setup of DMA, CPC and sp-ICP-MS with increased versatility

Accurate mass measurements of aerosol nanoparticles are inherently challenging. Beyond pure mass determination, such as can be realized using centrifugal particle mass analysis, aerosol mass spectrometry also enables material-specific analysis. In this work, the hyphenation of an inductively coupled plasma mass spectrometer working in single particle mode (sp-ICP-MS) with a scanning mobility particle sizer (SMPS) is presented. The coupling of the instruments is described, with special attention to the position of the gas exchange device, which allows flexible interconnection of DMA and ICP-MS while maintaining the full classification range of the DMA. The mass calibration of the ICP-MS signal and the limits in terms of particle concentration were studied on spherical gold nanoparticles. As an application example, the structure of gold nanoparticle agglomerates was characterized as a function of a preceding temperature treatment. The fractal dimension and the effective density of the agglomerates is directly determined after sintering at various temperatures. In addition, a new approach to derive the primary particle diameter from the measurement of agglomerate mass is outlined. Finally, the possibility of analyzing the particle charge is shown in perspective.

High resolution mass spectrometry method for the determination of 13 antibiotic groups in bovine, swine, poultry and fish meat: An effective screening and confirmation analysis approach for routine laboratories

A screening and confirmatory method for the determination of 13 antibiotic groups including 91 substances was developed for muscle samples and validated using ultra-performance liquid chromatography (UPLC) coupled to time-of-flight mass spectrometry. Optimisation of the parameters was performed for every analyte and personal compound database library was created, comprising the mass spectra for following collision energies; 0, 10, 20 and 40 eV. Validation plan scheming and calculation of the parameters was performed using validation software, which included following performance characteristics; selectivity, trueness, precision, decision limit (CCα), detection capability (CCβ) and relative matrix effect. High resolution mass spectrometry operated in a narrow mass window and resolving power of 50,000 FWHM (2 GHz). Accurate mass measurements with mass accuracy below 10 ppm for all analytes were obtained in spiked muscle samples. The validation experiments showed good selectivity and specificity. The method was validated in the measurement range from 0.5 to 1000 μg/kg, where a specific analyte mixed standard solution was prepared depending on the defined maximum residue limit (MRL) or lowest calibration level (LCL). For screening analysis, detection capabilities (CCβ) below the set MRL values or at LCL concentration levels were defined. CCβ, as the concentration above which the sample can be considered suspect, ranged from 0.63 to 207.8 μg/kg. For confirmation of the analyte, CCα was calculated at LCL or at the MRL, where it ranged from 0.38 to 14.3 μg/kg for unauthorised substances and from 13.8 to 1492.6 μg/kg for authorised substances. Relative within-laboratory reproducibility standard deviation ranged from 5.1 to 34.2%. Satisfactory z-score values in the range from −0.87 to 1.88 were obtained as a result of participating in four proficiency tests organized by European Union Reference Laboratories. • Screening and confirmatory HRMS method for 91 antibiotics. • Wide validation range around the established residue limits. • CCβ and CCα as parameters for screening and confirmatory analysis. • Satisfactory proficiency results as confirmation of good method performance.

Pharmaceuticals are identified in insects in River Fyris – A study with both tandem quadrupole and quadrupole-time-of-flight mass spectrometry

The internal concentrations of active pharmaceutical compounds in insects/macroinvertebrates in River Fyris, Uppsala, Sweden, have for the first time been investigated. Specimen of backswimmer, caddisfly larva, damselfly larva, mayfly larva and water louse were caught in the river downstream a waste-water treatment plant. After homogenization and extraction, analysis was carried out with Ultra-High Performance Liquid Chromatography – Electrospray – Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) using both a tandem quadrupole (QqQ) and a quadrupole-time-of-flight (qToF) mass spectrometer. A combined qualitative/quantitative screening method for 89 pharmaceutical compounds in the selective reaction monitoring mode was applied to the samples using the QqQ instrument. Thirty-three different drugs were detected and quantified in the macroinvertebrate samples, covering a wide range of pharmacological classes, the most common being antidepressants, psycholeptics and antihistamines. Drug concentrations up to 260 ng/g (for tetracycline) were determined. A subset of thirteen compounds were selected for a complementary qualitative UHPLC-qToF-MS/MS analysis. This way, the confidence in the substance identifications was significantly strengthened by the availability of full scan high-resolution spectra and accurate mass measurements. This is the first study demonstrating the uptake of pharmaceuticals in water-living macroinvertebrates in Sweden. Since these organisms are in the lower part of the food chain, pharmaceuticals might accumulate in predators leading to ecotoxicological effect at higher trophic levels. Macroinvertebrates might be promising indicator organisms for pharmaceutical pollution.

Simultaneous Method Development and Validation of Anastrozole Along with Piperine: Degradation Studies and Degradants Characterization Using LC-QTOF-ESI-MS Along with In-silico ADMET Predictions.

Anastrozole (ATZ) is a selective non-steroidal inhibitor widely used for the treatment of breast cancer in post-menopausal women. ATZ exerts its biological activity by inhibiting the enzyme aromatase, which is responsible for converting androgens to estrogens. Piperine (PIP), a natural alkaloid and the main component of black pepper, is used as a bioenhancer and for combating a variety of health issues ranging from upset stomach to dental problems. ATZ has been reported to have poor water solubility and less bioavailability. The novel combination of ATZ and PIP was proposed to enhance the bioavailability of both the compounds. However, there are no reported studies on the simultaneous estimation of ATZ and PIP as well as stability studies to explore their potential interactions and degradation profiling. A simple, accurate, precise, robust, sensitive, reliable, and economic analytical method for the simultaneous estimation of ATZ and PIP was developed using acetonitrile and water (60:40) as the mobile phase. Forced degradation studies and characterization of degradants were performed, and degradants were identified for molecular weight using LC-QTOF-ESI-MS; the structures of degradants were confirmed with mass accuracy measurements. The mechanism of each degradant has also been described in more detail in the manuscript. A total of fourteen degradants were characterized and reported for their good human oral absorption. A precise, robust, accurate, cheap, and sensitive RP-HPLC-DAD simultaneous method for the estimation of ATZ and PIP has been developed. From the future point of view, there is huge scope to conduct pharmacological, pharmacodynamic, and drug-herb interaction studies based on this fruitful outcome. All the degradants may be screened against MDR-resistant breast cancer in the future to check their potential as a drug target.

Combining Isotopologue Workflows and Simultaneous Multidimensional Separations to Detect, Identify, and Validate Metabolites in Untargeted Analyses.

While the combination of liquid chromatography and tandem mass spectrometry (LC-MS/MS) is commonly used for feature annotation in untargeted omics experiments, ensuring these prioritized features originate from endogenous metabolism remains challenging. Isotopologue workflows, such as isotopic ratio outlier analysis (IROA), mass isotopomer ratio analysis of U-13C labeled extracts (MIRACLE), and credentialing incorporate isotopic labels directly into metabolic precursors, guaranteeing that all features of interest are unequivocal byproducts of cellular metabolism. Furthermore, comprehensive separation and annotation of small molecules continue to challenge the metabolomics field, particularly for isomeric systems. In this paper, we evaluate the analytical utility of incorporating ion mobility spectrometry (IMS) as an additional separation mechanism into standard LC-MS/MS isotopologue workflows. Since isotopically labeled molecules codrift in the IMS dimension with their 12C versions, LC-IMS-CID-MS provides four dimensions (LC, IMS, MS, and MS/MS) to directly investigate the metabolic activity of prioritized untargeted features. Here, we demonstrate this additional selectivity by showcasing how a preliminary data set of 30 endogeneous metabolites are putatively annotated from isotopically labeled Escherichia coli cultures when analyzed by LC-IMS-CID-MS. Metabolite annotations were based on several molecular descriptors, including accurate mass measurement, carbon number, annotated fragmentation spectra, and collision cross section (CCS), collectively illustrating the importance of incorporating IMS into isotopologue workflows. Overall, our results highlight the enhanced separation space and increased annotation confidence afforded by IMS for metabolic characterization and provide a unique perspective for future developments in isotopically labeled MS experiments.

Phase Ⅰ and phase Ⅱ metabolic studies of Citrus flavonoids based on electrochemical simulation and in vitro methods by EC-Q-TOF/MS and HPLC-Q-TOF/MS

The oxidation products and metabolic pathways of five Citrus flavonoids were studied by online electrochemical/quadrupole time-of-flight mass spectrometry (EC/Q-TOF/MS). The simulated oxidation metabolism of target compounds in phase I and phase Ⅱ was carried out at boron-doped diamond (BDD) working electrode. The results obtained by EC-MS were compared with the conventional metabolism of rats and humans reported in previous literatures. In addition, the method of incubating the target compounds with rat liver microsomes in vitro was established, the target compounds and their metabolites were analyzed by high performance liquid chromatography coupled mass spectrometry. The structures of the metabolites were determined by accurate mass measurements and previous in vivo metabolite results. The results showed that the electrochemical oxidation metabolites were consistent with the results of in vitro incubation of liver microsomes, and also with the results reported in other literatures. As a consequence, EC/Q-TOF/MS is a promising and effective tool for studying metabolic transformation of different complex food components.

UHPLC-Q-TOF-MS/MS-based metabolite profiling of duvelisib and establishment of its metabolism mechanisms.

Duvelisib is a dual inhibitor of phosphoinositide 3 kinase that received global approval by the US Food and Drug Administration in 2018 to treat follicular lymphoma after at least two prior systemic therapies. An extensive literature search revealed that, to date, metabolites of duvelisib have not been characterized and information on them is not available in any of the literature. Moreover, the metabolism pathway is yet to be established. This study aimed to investigate and characterize the metabolites of duvelisib generated in microsomes and S9 fractions. In this study, five duvelisib metabolites were identified using UHPLC-Q-TOF-MS/MS analysis technique. The structural characterization of the metabolites was performed by comparing the fragmentation pattern of duvelisib and its metabolites through an accurate mass measurement technique. Three metabolites were generated through phase I hydroxylation and dechlorination reactions. The other two metabolites were generated through a phase II glucuronidation reaction. The metabolism mechanism established through this study can be useful to improve the safety profile of drugs of similar categories in the future after establishment of the toxicity profile of the identified metabolites.

Headspace-Low Water Absorption Trap Technique: Analysis of Low-Abundance Volatile Compounds from Fresh Artemisia Annua L. with GC-MS.

Conventional headspace (HS) method could not meet the requirement of analyzing low-abundance volatile compounds in high water content samples. A HS-low water absorption trap technique coupled with gas chromatography-mass spectrometry was introduced to remove the large amount of water vapor; therefore, the low-abundance volatile compounds could be detected with better analytical sensitivity. With this method, a total of 81 volatile compounds were identified from fresh Artemisia annua L. by mass spectral library search, retention index and accurate mass measurement, which could make the qualitative results more accurate and reliable. These compounds belonged to different species, including terpene, cycloparaffin, aliphatic aldehyde, aromatic ketone, aromatic aldehyde and so on. The 2,5,6-trimethyl-1,3,6-heptatriene (8.23%) was the most principal compound, followed by γ-muurolene (6.80%), β-caryophyllenea (6.24%), 1,8-cineol (5.76%), 2-carene (5.65%), borneol (5.57%), isocaryophyllene (4.91%), bornylene (4.78%), camphene (4.30%) and β-pinene (4.26%) as the main components. The results indicated that this method presents a great potential for the trace analysis of volatile compounds in complex high water content samples.

Rapid evaluation of particle size distribution using image analyzer with machine learning

Particle size distribution of soil is often evaluated by “the method for particle size distribution of soils (JIS A 1204)”. This method requires long sieving time and accurate mass measurement of sieved soils, resulting rapid evaluation of in-situ soil characteristics and admission decision of soil classification difficult. Image analysis using an image analyzer, developed by Marui Co. and named “Sand measure”, has been applied for rapid evaluation. The method holds the error generated by the overlaps of soil particles. We have applied machine learning with expanding the input data to image analyzer for reducing the error. The machine learning is installed in the model composed of Convolution Neural Network. The machine learning reduces the error by about 40 % of the results evaluated by test data. Maximum reduction in error is about 78 % in test data. The image analyzer with machine learning can be applicable for rapid evaluation of particle size distribution.

Proteoform Identification and Quantification Using Intact Protein Database Search Engine ProteinGoggle.

Proteomics studies the proteome of organisms, especially proteins that are differentially expressed under certain physiological or pathological conditions; qualitative identification of protein sequences and posttranslational modifications (PTMs) and their positions can help us systematically understand the structure and function of proteoforms. With the development and relative popularity of soft ionization technology (such as electrospray ionization technology) and high mass measurement accuracy and high-resolution mass spectrometers (such as orbitrap), the mass spectrometry (MS) characterization of complete proteins (the so-called top-down proteomics) has become possible and has gradually become popular. Corresponding database search engines and protein identification bioinformatics tools have also been greatly developed. This chapter provides a brief overview of intact protein database search algorithm "isotopic mass-to-charge ratio and envelope fingerprinting" and search engine ProteinGoggle.

Dereplication of a Dichloromethane Extract of Goniothalamus lanceolatus Leaves using UHPLC-ESI-ORBITRAP HRMS

In our continuing search for bioactive compounds in Goniothalamus lanceolatus, we scrutinized the chemical constituents present in the leaves of this plant. As these leaves are traditionally used to repel mosquitoes, we were inspired to examine the plant for potential anti-dengue activity. Our preliminary screening showed that at a concentration of 50 µg/ml, the dichloromethane extract of these leaves was able to inhibit 90.9% of Dengue Virus Type-2 (DENV-2). Dose-dependent plaque assays gave an IC50 of 4.16 µg/ml with a selectivity index (SI) of 5.82. Thus, this extract was selected for in-depth phytochemical analysis. This paper reports an efficient chemical profiling of the G. lanceolatus leaf dichloromethane extract using high-resolution mass spectrometry (UHPLC-ESI-Orbitrap), via data-dependent MS/MS experiments. We used MZmine2 software version 2.50 (MZmine2) for data processing and peak deconvolution. The dereplication strategy began with the determination of molecular formula from accurate mass measurements (m/z). Data mining using MZmine2 followed by cross-search filters against the Dictionary of Natural Products (DNP) produced several hits consisting of styryl-lactones, alkaloids, and acetogenins. A further search of the molecular formula of isolated compounds from different parts of G. lanceolatus using an in-house library unambiguously identified seven compounds including goniolanceolatin A, goniolanceolatin E, (6S,7S,8S)-goniodiol, 1S,5S,7R,8S,3-exo,7-endo-(+)-8-epi-9-deoxygoniopypyrone, goniofupyrone B, parvistone D, and deoxygoniopypyrone B.

Rapid Identification of 3,6'-Disinapoyl Sucrose Metabolites in Alzheimer's Disease Model Mice Using UHPLC-Orbitrap Mass Spectrometry.

Alzheimer’s disease (AD) is a degenerative disease of the central nervous system characterized by the progressive impairment of neural activity. Studies have shown that 3,6′-disinapoyl sucrose (DISS) can alleviate the pathological symptoms of AD through the activation of the cAMP/CREB/BDNF signaling pathway. However, the exact biochemical mechanisms of action of DISS are not clear. This study explores metabolism of DISS in an AD mouse model, induced by the microinjection of a lentiviral expression plasmid of the APPswe695 gene into CA1 of the hippocampus. After gavage administration of DISS (200 mg/kg), the kidneys, livers, brains, plasma, urine, and feces were collected for UHPLC–Orbitrap mass spectrometry analysis. Twenty metabolites, including the prototype drug of DISS, were positively or tentatively identified based on accurate mass measurements, characteristic fragmentation behaviors, and retention times. Thus, the metabolic pathways of DISS in AD mice were preliminarily elucidated through the identification of metabolites, such as ester bond cleavage, demethoxylation, demethylation, and sinapic acid-related products. Furthermore, differences in the in vivo distribution of several metabolites were observed between the model and sham control groups. These findings can provide a valuable reference for the pharmacological mechanisms and biosafety of DISS.

Revealing the Toxicity-Enhancing Essence of Glycyrrhiza on Genkwa Flos Based on Ultra-high-performance Liquid Chromatography Coupled With Quadrupole-Orbitrap High-Resolution Mass Spectrometry and Self-Assembled Supramolecular Technology.

Researchers often focus on the mechanisms of synergistic agents, a few explore drug combinations that enhance toxicity, while few have studied the internal mechanism of compatibility enhancement in chemical level. Herein, we present a comprehensive analysis based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and a self-assembled supramolecular strategy, which reveals the toxicity-enhancing essence of glycyrrhizic acid originated in licorice when combined with Genkwa Flos. Through this method, we discovered the toxicity was enhanced through the formation of a supramolecular complex from Genkwa Flos/glycyrrhizic acid. The morphology and size distribution of the self-assembled nanoparticles were characterized by scanning electron microscopy and dynamic light scattering Furthermore, a total of 58 constituents (eight diterpenoids, 35 flavonoids, five phenylpropanoids, four nucleosides, two amino acids, and four other compounds) consisted from the supramolecular complex were identified through accurate-mass measurements in full-scan MS/data-dependent MS/MS mode. Based on the hydrophobic interaction of glycyrrhizic acid with yuanhuacine (one of main ingredients from Genkwa Flos), the supramolecular self-assembly mechanism was revealed with proton nuclear magnetic resonance (1H-NMR) and NOESY 2D NMR. The toxicity of Genkwa Flos and Genkwa Flos/glycyrrhizic acid supramolecular complex were compared through in vitro studies on L-02 cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and 4′,6-diamidino-2-phenylindole (DAPI) staining was performed to further confirm the enhancement inhibition of Genkwa Flos/glycyrrhizic acid supramolecular complex than Genkwa Flos. This study provides fundamental scientific evidence of the formation of a self-assembled phytochemical supramolecular when Genkwa Flos and glycyrrhizic acid are combined, enabling to understand their clinical incompatibility and contraindication.