Stepped-up development of accelerator mass spectrometry method for the detection of ^(60)Fe with the HI-13 tandem accelerator

The Moon provides a unique environment for investigating nearby astrophysical events such as supernovae.Lunar samples retain valuable information from these events,via detectable long-lived“fingerprint”radionuclides such as^(60)Fe.In this work,we stepped up the development of an accelerator mass spectrometry(AMS)method for detecting^(60)Fe using the HI-13tandem accelerator at the China Institute of Atomic Energy(CIAE).Since interferences could not be sufficiently removed solely with the existing magnetic systems of the tandem accelerator and the following Q3D magnetic spectrograph,a Wien filter with a maximum voltage of±60 kV and a maximum magnetic field of 0.3 T was installed after the accelerator magnetic systems to lower the detection background for the low abundance nuclide^(60)Fe.A 1μm thick Si_(3)N_(4) foil was installed in front of the Q3D as an energy degrader.For particle detection,a multi-anode gas ionization chamber was mounted at the center of the focal plane of the spectrograph.Finally,an^(60)Fe sample with an abundance of 1.125×10^(-10)was used to test the new AMS system.These results indicate that^(60)Fe can be clearly distinguished from the isobar^(60)Ni.The sensitivity was assessed to be better than 4.3×10^(-14)based on blank sample measurements lasting 5.8 h,and the sensitivity could,in principle,be expected to be approximately 2.5×10^(-15)when the data were accumulated for 100 h,which is feasible for future lunar sample measurements because the main contaminants were sufficiently separated.

Determination of Ten Kinds of Alpha-2 Agonists Residues in Animal Derived Food by UHPLC-Triple Quadrupole/Composite Linear Ion Trap Mass Spectrometry

[Objectives]The paper was to establish an ultra high performance liquid chromatography-quadrupole/linear ion trap complex mass spectrometry for the determination of 10 kinds ofα2-receptor agonists in animal derived food.[Methods]The samples were extracted with sodium carbonate buffer solution and ethyl acetate,and analyzed by mass spectrometry after solid phase extraction and high performance liquid chromatography separation.[Results]Ten kinds ofα2-receptor agonists showed a good linear relationship in the range of 1-100μg/mL,with the average recovery of over 69%and the relative standard deviation less than 8.32%.The detection limit of 10 kinds of α_(2)-receptor agonists was up to 1μg/kg.[Conclusions]The method has good selectivity and strong anti-interference ability,and can meet the requirements of 10 kinds ofα2-receptor agonists residues in animal derived food.

Research on the Upper Limit of Accuracy for Predicting Theoretical Tandem Mass Spectrometry

In recent years, numerous theoretical tandem mass spectrometry prediction methods have been proposed, yet a systematic study and evaluation of their theoretical accuracy limits have not been conducted. If the accuracy of current methods approaches this limit, further exploration of new prediction techniques may become redundant. Conversely, a need for more precise prediction methods or models may be indicated. In this study, we have experimentally analyzed the limits of accuracy at different numbers of ions and parameters using repeated spectral pairs and integrating various similarity metrics. Results show significant achievements in accuracy for backbone ion methods with room for improvement. In contrast, full-spectrum prediction methods exhibit greater potential relative to the theoretical accuracy limit. Additionally, findings highlight the significant impact of normalized collision energy and instrument type on prediction accuracy, underscoring the importance of considering these factors in future theoretical tandem mass spectrometry predictions.

Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.

Evaluation of allergenic protein profiles in three Chinese high-oleic acid peanut cultivars using NanoLC-Orbitrap mass spectrometry

High oleic-acid peanuts are known for their pre-longed shelf-life and health benefit due to high content of oleic fatty acid.However,the allergenicity and allergenic protein profiles in Chinese high-oleic peanuts have yet to be studied.For this purpose,an Orbitrap Fusion mass spectrometry(MS)-based method that is feasible for identification of putative allergenic protein as well as semi-quantitation of five major allergen protein in three different Chinese high-oleic peanut cultivars(JH 13,JH 16 and JH 18)have been reported.Results show that three Chinese high-oleic acid peanut cultivars selected all contained highly allergenic proteins Ara h1,Ara h 2,Ara h 3 and Ara h 6.The allergenic protein profiles of Chinese high-oleic acid peanut cultivars were very similar to that of conventional peanuts,but the allergenic protein subunits varied greatly among higholeic peanuts.Additionally,a comprehensive peptide-filtering pipeline had been developed for identification of potential peptide markers in peanut allergen proteins.Through the peptide-filtering pipeline,three novel peptide markers,IVQIEAKPNTLVLPK,SSNPDIYNPQAGSLR and AQSENYEYLAFK surrogate to Ara h 1,Ara h 3 with high abundance,good MS response and highly reliability were identified,which can be used as candidate peptide markers for the detection of peanut allergens in different food matrices.

Nylon 6-cellulose composite hosted in a hypodermic needle: Biofluid extraction and analysis by ambient mass spectrometry in a single device

This study proposes a hypodermic needle(HN)as a sorbent holder and an electrospray(ESI)emitter,thus combining extraction and analysis in a single device.A novel nylon 6-cellulose(N6-Cel)composite sorbent is proposed to extract methadone from oral fluid samples.The cellulosic substrate provides the composite with high porosity,permitting the flow-through of the sample,while the polyamide contributes to the extraction of the analyte.The low price of the devices(considering the holder and the sorbent)contributes to the affordability of the method,and their small size allows easy transportation,opening the door to on-site extractions.Under the optimum conditions,the analyte can be determined by high-resolution ambient ionization mass spectrometry at a limit of detection(LOD)as low as 0.3 mg/L and precision(expressed as relative standard deviation,RSD)better than 9.3%.The trueness,expressed as relative recovery(RR),ranged from 90%to 109%.As high-resolution mass spectrometers are not available in many laboratories,the method was also adapted to low-resolution spectrometers.In this sense,the direct infusion of the eluates in a triple quadrupole-mass spectrometry provided an LOD of 2.2 mg/L.The RSD was better than 5.3%,and the RR ranged from 96%to 121%.

Tracking gassing behavior in pouch cell by operando on-line electrochemical mass spectrometry

As the rapid development of more powerful and safer lithiumion batteries, the mechanism study of gases evolution is attacking more and more attention in recent years. Especially under overcharge/discharge and/or high-temperature working condition.

Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid

Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors

During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

Rapid authentication of different herbal medicines by heating online extraction electrospray ionization mass spectrometry

The rapid and accurate authentication of traditional Chinese medicines(TCMs)has always been a key scientific and technical problem in the field of pharmaceutical analysis.Herein,a novel heating online extraction electrospray ionization mass spectrometry(H-oEESI-MS)was developed for the rapid and direct analysis of extremely complex substances without the requirement for any sample pretreatment or pre-separation steps.The overall molecular profile and fragment structure features of various herbal medicines could be completely captured within 10–15 s,with minimal sample(<0.5 mg)and solvent consumption(<20μL for one sample).Furthermore,a rapid differentiation and authentication strategy for TCMs based on H-oEESI-MS was proposed,including metabolic profile characterization,characteristic marker screening and identification,and multivariate statistical analysis model validation.In an analysis of 52 batches of seven types of Aconitum medicinal materials,20 and 21 key compounds were screened out as the characteristic markers of raw and processed Aconitum herbal medicines,respectively,and the possible structures of all the characteristic markers were comprehensively identified based on Compound Discoverer databases.Finally,multivariate statistical analysis showed that all the different types of herbal medicines were well differentiated and identified(R^(2)X>0.87,R^(2)Y>0.91,and Q^(2)>0.72),which further verified the feasibility and reliability of this comprehensive strategy for the rapid authentication of different TCMs based on H-oEESI-MS.In summary,this rapid authentication strategy realized the ultra-high-throughput,low-cost,and standardized detection of various complex TCMs for the first time,thereby demonstrating wide applicability and value for the development of quality standards for TCMs.

Comparison of different approaches for direct coupling of solid-phase microextraction to mass spectrometry for drugs of abuse analysis in plasma

The direct coupling of solid-phase microextraction(SPME)to mass spectrometry(MS)(SPME-MS)has proven to be an effective method for the fast screening and quantitative analysis of compounds in complex matrices such as blood and plasma.In recent years,our lab has developed three novel SPME-MS techniques:SPME-microfluidic open interface-MS(SPME-MOI-MS),coated blade spray-MS(CBS-MS),and SPME-probe electrospray ionization-MS(SPME-PESI-MS).The fast and high-throughput nature of these SPME-MS technologies makes them attractive options for point-of-care analysis and anti-doping testing.However,all these three techniques utilize different SPME geometries and were tested with different MS instruments.Lack of comparative data makes it difficult to determine which of these methodologies is the best option for any given application.This work fills this gap by making a comprehensive comparison of these three technologies with different SPME devices including SPME fibers,CBS blades,and SPME-PESI probes and SPME-liquid chromatography-MS(SPME-LC-MS)for the analysis of drugs of abuse using the same MS instrument.Furthermore,for the first time,we developed different desorption chambers for MOI-MS for coupling with SPME fibers,CBS blades,and SPME-PESI probes,thus illustrating the universality of this approach.In total,eight analytical methods were developed,with the experimental data showing that all the SPME-based methods provided good analytical performance with R^(2)of linearities larger than 0.9925,accuracies between 81%and 118%,and good precision with an RSD%≤13%.

Determination of Voriconazole in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in Therapeutic Drug Monitoring

A sensitive, accurate and robust Liquid Chromatography Tandem Mass Spectrometry method has been developed and validated to measure voriconazole trough levels in human plasma. The plasma samples were mixed with fluconazole as an Internal Standard and directed to protein precipitation and drug extraction. An aliquot of 1 μl was injected into the chromatographic system and separated by the Acquity BEH C18 column at a flow rate of 0.30 ml/min in a gradient mobile phase consisting of acetonitrile, Ultrapure water (UPW), methanol and formic acid. Voriconazole was detected by a Triple Quadrupole Detector (TQD) operating on Multiple Reaction Monitoring (MRM) and a positive ion mode Electrospray ionization (ESI) Q1 mass: 350.1 m/z, Q3 mass: 281.1 m/z. Method linearity of the calibration curve (0.10 - 8.00 μg/ml) indicated a correlation coefficient r ≥ 0.99. The intra and inter-assay accuracy was within 85% - 115% and the intra and inter-assay precision was ≤5.76%. Voriconazole recovery percentage was between 97.69 - 119.62%. The method was successively applied in routine voriconazole TDM.

Determination of egg and milk allergen in food products by liquid chromatography-tandem mass spectrometry based on signature peptides and isotope-labeled internal standard

The aim of this work was to develop a liquid chromatography-tandem mass spectrometry method for the determination of milk allergen and egg allergen in food products.Signature peptides GGLEPINFQTAADQAR,VGINYWLAHK,VLVLDTDYK,FFVAPFPEVFGK,and NAVPITPTLNR were confirmed and synthesized as the quantitative peptide of ovalbumin,α-lactalbumin,β-lactoglobulin,α_(S1)-casein andα_(S2)-casein,the relative isotope-labeled internal standards were used in the quantitative analysis.Linear range was in the range of0.5-5000.0 nmol/L for egg and milk allergen in bread,cake,cookie,rice crust and wheat flour samples with free from egg and milk,the limits of detection of milk allergens and egg allergen were in the range between0.94 mg/100 g and 56.71 mg/100 g,limits of quantification of milk allergens and egg allergen were in the range between 2.36 mg/100 g and 141.78 mg/100 g.The recoveries ranged from 76.7%to 122.8%,the relative standard deviations were in the range of 1.60%-15.60%.The developed method has been successfully used for the detection of egg and milk allergen in various food samples.

Simultaneous Determination of 14 β-Receptor Agonists Residues in Mutton by High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS)

[Objectives]A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established for the determination of 14β-receptor agonist residues in mutton.[Methods]Samples were hydrolyzed byβ-glucuronidase and extracted with 5%acetic acid-acetonitrile(1:99,V/V)solution.An Eclipse plus C 18 column was used for separation,and the MRM mode was used for qualitative analysis,and the external standard method was used for quantitative analysis of matrix standard solutions.[Results]Under the optimal conditions,the retention time of the 14 kinds ofβ-receptor agonists ranged from 1.0 to 9.5 min.When the mass concentration was in the range of 0.05-0.50μg/ml,the linear relationship ofβ-receptor agonists was good,with correlation coefficients(r)≥0.9992.The detection limits of the method were in the range of 0.04-0.87μg/kg,and the quantitative limits were in the range of 0.35-1.86μg/kg.The average recovery values were in the range of 82.8%-108.9%,with RSDs(n=6)in the range of 1.9%-6.7%.[Conclusions]The method is simple,sensitive,reproducible,accurate,and can be used for simultaneous determination of the 14 kinds ofβ-receptor agonist residues in mutton.

Determination of Oleuropein in Cosmetics by Ultra Performance Liquid Chromatography-Triple Quadrupole Tandem Mass Spectrometry

An ultrahigh performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS)was established to quickly and accurately determine the content of oleuropein in cosmetics.The samples were extracted with methanol-aqueous solution,and the mobile phase with methanol-formic acid solution(0.1 mol/L)=40∶60 was separated by Agilent ZORBAX Eclipse Plus C18(2.1 mm×50 mm×1.8μm-Micron)column temperature 30℃,flow rate 0.3 mL/min.The MS end was detected by electrospray negative mode ionization(ESI-)and multiple reaction monitoring(MRM)mode.The results show a good linear relationship in the range of 0.002~5 mg/L,with a correlation coefficient R2 of 0.999,5.Method recovery range from 84.2%~107.6%and the relative standard deviation RSD is 5.8%.The detection time is 5 min,the detection limit is 0.000,6 mg/L,and the limit of quantification is 0.002 mg/L.This method has the advantages of convenient operation,low quantification limit,high precision and good repeatability,and is suitable for measuring the content of oleuropein in many kinds of cosmetics.

Metabolomics of gastric cancer metastasis detected by gas chromatography and mass spectrometry

AIM:To elucidate the underlying mechanisms of metastasis and to identify the metabolomic markers of gastric cancer metastasis.METHODS:Gastric tumors from metastatic and nonmetastatic groups were used in this study.Metabolites and different metabolic patterns were analyzed by gas chromatography,mass spectrometry and principal components analysis (PCA),respectively.Differentiation performance was validated by the area under the curve (AUC) of receiver operating characteristic curves.RESULTS:Twenty-nine metabolites were differentially expressed in animal models of human gastric cancer.Of the 29 metabolites,20 were up-regulated and 9 were down-regulated in metastasis group compared to non-metastasis group.PCA models from the metabolite profiles could differentiate the metastatic from the nonmetastatic specimens with an AUC value of 1.0.These metabolites were mainly involved in several metabolic pathways,including glycolysis (lactic acid,alaline),serine metabolism (serine,phosphoserine),proline metabolism (proline),glutamic acid metabolism,tricarboxylic acid cycle (succinate,malic acid),nucleotide metabolism (pyrimidine),fatty acid metabolism (docosanoic acid,and octadecanoic acid),and methylation(glycine).The serine and proline metabolisms were highlighted during the progression of metastasis.CONCLUSION:Proline and serine metabolisms play an important role in metastasis.The metabolic profiling of tumor tissue can provide new biomarkers for the treatment of gastric cancer metastasis.

Recent advances in mass spectrometry-based proteomics of gastric cancer

The last decade has witnessed remarkable technological advances in mass spectrometry-based proteomics. The development of proteomics techniques has enabled the reliable analysis of complex proteomes, leading to the identification and quantification of thousands of proteins in gastric cancer cells, tissues, and sera. This quantitative information has been used to profile the anomalies in gastric cancer and provide insights into the pathogenic mechanism of the disease. In this review, we mainly focus on the advances in mass spectrometry and quantitative proteomics that were achieved in the last five years and how these up-andcoming technologies are employed to track biochemical changes in gastric cancer cells. We conclude by presenting a perspective on quantitative proteomics and its future applications in the clinic and translational gastric cancer research.

Simultaneous determination of amino acids in different teas using supercritical fluid chromatography coupled with single quadrupole mass spectrometry

Tea is a widely consumed beverage and has many important physiological properties and potential health benefits. In this study, a novel method based on supercritical fluid chromatography coupled with mass spectrometry (SFC-MS) was developed to simultaneously determine 11 amino acids in different types of tea (green teas, Oolong tea, black tea and Pu-erh tea). The separation conditions for the analysis of the selected amino acids including the column type, temperature and backpressure as well as the type of additive, were carefully optimized. The best separation of the 11 amino acids was obtained by adding water (5%, v/v) and trifluoroacetic acid (0.4%, v/v) to the organic modifier (methanol). Finally, the developed SFC-MS method was fully validated and successfully applied to the determination of these amino acids in six different tea samples. Good linearity (r ≥ 0.993), precision (RSDs≤ 2.99%), accuracy (91.95%-107.09%) as well as good sample stability were observed. The limits of detection ranged from 1.42 to 14.69 ng/mL, while the limits of quantification were between 4.53 and 47.0 ng/mL. The results indicate that the contents of the 11 amino acids in the six different tea samples are greatly influenced by the degree of fermentation. The proposed SFC-MS method shows a great potential for further investigation of tea varieties.

Gas chromatography/mass spectrometry based metabolomic study in a murine model of irritable bowel syndrome

AIM To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome(IBS).METHODS In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum(C. butyricum) treatment. C57 BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress(WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry(GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS(days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A(Co A) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways.CONCLUSION The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism.

Determination of urine catecholamines and metanephrines by reversed-phase liquid chromatography-tandem mass spectrometry

The measurement of urine catecholamine and metanephrine concentrations is important for biochemical screening and diagnosis of pheochromocytoma.The goal of this work was to develop a simple liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for determining catecholamines and metanephrines in urine to replace an existing liquid chromatographic method using electrochemical detection.Urine samples were prepared using Oasis weak-cation-exchange cartridges.The eluate was analyzed on an Agilent ZORBAX Eclipse Plus Phenyl-Hexyl column in 3 min.Adrenaline,noradrenaline,dopamine,metanephrine,normetanephrine,and their deuterated internal standards were monitored in positive electrospray ionization mode by multiple reaction monitoring(MRM).No evidence of ion suppression was observed.The assay was linear up to 5μmol/L for adrenaline,5μmol/L for noradrenaline,6.1μmol/L for dopamine,5.6μmol/L for metanephrine,and 34.6μmol/L for normetanephrine,with lower limits of quantification of 5,5,12,6 and 7nmol/L,respectively.The intra-day and inter-day precisions for all analytes ranged from 0.59%to 4.64%and1.98%to 4.80%,respectively.External quality assurance samples were assayed and showed excellent agreement with the target values.This simple method provides an improved assay for determining urine catecholamines and metanephrines.