Ultra-performance Liquid Chromatography-high Resolution Mass Research Articles

Multisample lipidomic profiles of irritable bowel syndrome and irritable bowel syndrome-like symptoms in patients with inflammatory bowel disease: new insight into the recognition of the same symptoms in different diseases.

Overlapping clinical manifestations of irritable bowel syndrome (IBS) and IBS-like symptoms in patients with inflammatory bowel disease (IBD-IBS) present challenges in diagnosis and management. Both conditions are associated with alterations in metabolites, but few studies have described the lipid profiles. Our aim was to pinpoint specific lipids that contribute to the pathogenesis of IBS and IBD-IBS by analyzing multiple biologic samples. Diarrhea-predominant IBS (IBS-D) patients (n = 39), ulcerative colitis in remission with IBS-like symptoms patients (UCR-IBS) (n = 21), and healthy volunteers (n = 35) were recruited. IBS-D patients meet the Rome IV diagnostic criteria, and UCR-IBS patients matched mayo scores ≤ two points and Rome IV diagnostic criteria. Serum, feces, and mucosa were collected for further analysis. Lipid extraction was carried out by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Lipidomics of mucosa and serum samples significantly differed among the three groups. Feces showed the most altered lipid species, and the enrichment analysis of 347 differentially abundant metabolites via KEGG pathway analysis revealed that alpha-linolenic acid metabolism was significantly altered in the two groups (P < 0.01). The ratio of omega-6/omega-3 fatty acid were imbalance in serum samples. This study revealed a comprehensive lipid composition pattern between IBS-D patients and UCR-IBS patients. We found several distinctive lipids involved in alpha-linolenic acid metabolism, reflecting an imbalance in the omega-6/omega-3 fatty acid ratio. Compared to mucosa and serum samples, fecal samples might have more advantages in lipidomics studies due to the convenience of sample collection and effectiveness in reflecting metabolic information.

Metabolomics analysis reveals characteristic metabolites in different levels of oxaliplatin-induced neurotoxicity.

Oxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.

Elevated Temperature Effects on Protein Turnover Dynamics in Arabidopsis thaliana Seedlings Revealed by 15N-Stable Isotope Labeling and ProteinTurnover Algorithm.

Global warming poses a threat to plant survival, impacting growth and agricultural yield. Protein turnover, a critical regulatory mechanism balancing protein synthesis and degradation, is crucial for the cellular response to environmental changes. We investigated the effects of elevated temperature on proteome dynamics in Arabidopsis thaliana seedlings using 15N-stable isotope labeling and ultra-performance liquid chromatography-high resolution mass spectrometry, coupled with the ProteinTurnover algorithm. Analyzing different cellular fractions from plants grown under 22 °C and 30 °C growth conditions, we found significant changes in the turnover rates of 571 proteins, with a median 1.4-fold increase, indicating accelerated protein dynamics under thermal stress. Notably, soluble root fraction proteins exhibited smaller turnover changes, suggesting tissue-specific adaptations. Significant turnover alterations occurred with redox signaling, stress response, protein folding, secondary metabolism, and photorespiration, indicating complex responses enhancing plant thermal resilience. Conversely, proteins involved in carbohydrate metabolism and mitochondrial ATP synthesis showed minimal changes, highlighting their stability. This analysis highlights the intricate balance between proteome stability and adaptability, advancing our understanding of plant responses to heat stress and supporting the development of improved thermotolerant crops.

Exploring the antimicrobial activity of Origanum majorana L. against the highly virulent multidrug-resistant Acinetobacter baumannii AB5075: UPLC-HRMS profiling with in vitro and in silico studies

BackgroundThe infamous multidrug-resistant (MDR) bacterium Acinetobacter baumannii is becoming a nightmare in intensive care units across the globe. Since there are now very few effective antimicrobial agents, it is necessary to explore unconventional resources for novel antimicrobials. This study investigated the potential antimicrobial activity of Origanum majorana L. against A. baumannii employing multiple approaches including antimicrobial susceptibility, fractionation, ultra-performance liquid chromatography–high-resolution mass spectrometry (UPLC-HRMS) dereplication, and in silico analysis for target/ligand identification.ResultsOn the extremely pathogenic MDR strain A. baumannii AB5075, O. majorana L. has shown a significant growth inhibitory effect (MIC = 0.675 mg/mL). The polar 50% methanol fraction was the most active (MIC = 0.5 mg/mL). The UPLC-HRMS dereplication of the bioactive fraction detected 29 metabolites belonging to different chemical classes. Justicidin B, one of the identified metabolites, was projected by preliminary in silico analysis to be the most highly scoring metabolite for binding with molecular targets in A. baumannii with a Fit score = 8.56 for enoyl-ACP reductase (FabI) (PDB ID: 6AHE), suggesting it to be its potential target. Additionally, docking, molecular dynamics simulation, and bioinformatics analysis suggested that this interaction is similar to a well-known FabI inhibitor. The amino acids involved in the interaction are conserved among different MDR A. baumannii strains and the effectiveness could extend to Gram-negative pathogens within the ESKAPE group.ConclusionsOriganum majorana L. extract exhibits antimicrobial activity against A. baumannii using one or more metabolites in its 50% methanol fraction. The characterized active metabolite is hypothesized to be justicidin B which inhibits the growth of A. baumannii AB5075 via targeting its fatty acid synthesis.

Novel Identification of Cysteinyl Derivatives of Toxic Clozapine Nitrenium Ions and the Effect of Valproic Acid on Metabolite Formation: A Study Using Reprocessed High-Resolution Mass Spectra of Analyzed Therapeutic Drug Monitoring Samples.

Clozapine (CLZ) use is hampered by the risk of granulocyte toxicity, which is associated with the formation of nitrenium ions and the concurrent use of valproic acid (VPA). These highly reactive nitrenium ions cannot be measured in vivo. Instead, deactivated cysteinyl conjugates may potentially be detected. The aim of this study was to develop a novel method for identifying cysteinylated derivates of CLZ nitrenium ions to investigate the effect of VPA on their formation using therapeutic drug monitoring data. A population comprising 93 VPA comedicated and 162 control patients from a therapeutic drug monitoring (TDM) service in Oslo, Norway, was included. Reprocessing of ultraperformance liquid chromatography high-resolution mass spectra (UHPLC-HR-MS) of previously analyzed TDM samples, combined with the assessment of MS/MS fragmentation patterns, was performed to identify the CLZ cysteinyl conjugates. Smoking, which induces CLZ metabolism, was assessed by detecting cotinine in the reprocessed mass spectra. By reprocessing the UHPLC-HR-MS files of the TDM analyses and reviewing the MS/MS fragment profiles, four cysteinyl conjugates of CLZ were identified. The formations of CLZ cysteinyl (CLZ-Cys 1+ ) and CLZ- N -oxide cysteinyl (CLZ-NOX-Cys 1+ ) were 1.5-fold ( P = 0.038) and 2.1-fold ( P < 0.001) higher in VPA-treated patients than those in the controls. In agreement with previous studies, a 45% reduction in N -desmethylclozapine formation was observed in VPA-treated patients ( P < 0.001). A novel method for detecting cysteinyl conjugates of CLZ was developed. Application of this method indicated that VPA significantly increased the formation of CLZ-Cys 1+ metabolites, which might explain the granulocyte toxicity reported after adding VPA to CLZ treatment. The developed method opens new avenues for investigating CLZ toxicity, e.g. by correlating cysteinyl conjugates and granulocyte counts in patients.

Surface multi-walled carbon nanotube modified quaternary amine-functionalized polymers for purification and determination of glyphosate and its four metabolites in plasma samples

The present study focused on the pretreatment and detection of GLY and its four metabolites AMPA, N-acetyl AMPA, N-methyl GLY and N-acetyl GLY in plasma samples. Multi-walled carbon nanotube-modified quaternary amine-functionalized polymers (QA-PDNV@MWCNTs) were synthesized in a controlled manner by self-assembly, and its morphology and composition were extensively characterized. The QA-PDNV@MWCNTs microspheres were then used as an SPE adsorbent for the preparation and rapid determination of GLY and its four metabolites in plasma samples combined with ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). The SPE conditions based on QA-PDNV@MWCNTs were optimized for GLY and its metabolites to obtain the best purification efficiency. The experimental results show that when the adsorbent contains 8% MWCNTs, it can balance the adsorption of target analytes and the purification performance of the adsorbent for impurities. In addition, this study compared the QA-PDNV@MWCNTs based SPE method with the commercial Waters Oasis MAX SPE cartridge and the results showed that the developed method in this study has better resistance to matrix interference. Under optimal conditions, the recoveries of GLY and its metabolites spiked in plasma were 82.6-99.4% with relative standard deviations (RSDs) of 1.0-7.8%. The limits of detection (LODs, S/N≥3) and limits of quantification (LOQs, S/N≥9) of the method were 0.05-0.33 μg/L and 0.15-1.00 μg/L, respectively. Finally, the developed QA-PDNV@MWCNTs based SPE-UPLC-HRMS method was used to confirm GLY poisoning not only on the basis of the detection of the GLY prototype, but also on the basis of its four metabolites.

In vivo pharmacokinetic study of vanillic acid in monocrotaline-induced pulmonary arterial hypertension rats and its tissue distribution.

Vanillic acid (VA) is a bioactive chemical present in many food plants and fruits. It has been shown to have a protective effect on pulmonary tissues in monocrotaline-induced pulmonary arterial hypertension, as well as an intervention effect on right ventricular remodeling. The purpose of this study was to develop and test a reliable method for assessing VA utilizing ultra-performance liquid chromatography-high resolution mass spectrometry using caffeic acid as the internal standard. Across diverse substrates, the correlation coefficient for VA ranged from 0.9992 to 0.9995. The method's intraday precision was <13.53% (RSD), and its accuracy (RE) ranged from -9.88 to 4.35%. The precision across days was <13.69% (RSD), while the accuracy ranged from 2.16 to 10.94% (RE). The extraction recoveries ranged from 80.30 to 118.81%, with a lower limit of quantification of 20 ng/mL. The approach was successfully applied to pharmacokinetic and tissue distribution studies of VA in rat plasma after gavage administration, and the pharmacokinetic parameters of VA in the plasma of the monocrotaline-induced pulmonary arterial hypertension were significantly different from those of the control group.

Detection of three metabolites of xylene in urine samples by solid-phase extraction coupled with liquid chromatography-mass spectrometry

Objective: To establish a method for the rapid determination of the three metabolites of xylene, 2-methylmarmaluronic acid, 3-methylmarmaluronic acid and 4-methylmarmaluronic acid, in urine of occupationally exposed workers by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) . Methods: In July 2022, urine samples were diluted and extracted with pH=6.86 phosphate cache solution, cleaned up by a MAX solid-phase extraction (SPE) column and separated by an Accucore Ph/Hexyl column (100 mm×2.1 mm, 2.6 μm) with a gradient of 5 mmol/L ammonium formate-0.1% formic acid aqueous solution and methanol as mobile phases. The analysis was carried out in electrospray ionization mode and full mass-data dependent secondary mass spectrometry mode, and quantified by external standard method. The characteristics of each index of this method were analyzed. Results: A good linearity was obtained in the concentration range of 1.0-200.0 μg/L for 2-methylmuramic acid, 3-methylmuramic acid and 4-methylmuramic acid with the correlation coefficients of 0.9979-0.9993. The limits of detection of the method were 0.18-0.24 μg/L. While the spiked recoveries at the three concentrations (1.0 μg/L, 100.0 μg/L, and 180.0 μg/L) were in the range of 83.0%-93.7%, with the relative standard deviations of 2.2%-7.9%. Conclusion: The UPLC-HRMS method is simple, rapid, sensitive and accurate, and is suitable for the simultaneous determination of the three metabolites of xylene in the urine of occupationally exposed workers.

LC-MS-based serum metabolomics analysis for the screening and monitoring of colorectal cancer.

Colorectal Cancer (CRC) is a prevalent digestive system tumour with significant mortality and recurrence rates. Serum metabolomics, with its high sensitivity and high throughput, has shown potential as a tool to discover biomarkers for clinical screening and monitoring of the CRC patients. Serum metabolites of 61 sex and age-matched healthy controls and 62 CRC patients (before and after surgical intervention) were analyzed using a ultra-performance liquid chromatography-high resolution mass spectrometer (UPLC-MS). Statistical methods and pathway enrichment analysis were used to identify potential biomarkers and altered metabolic pathways. Our analysis revealed a clear distinction in the serum metabolic profile between CRC patients and healthy controls (HCs). Pathway analysis indicated a significant association with arginine biosynthesis, pyrimidine metabolism, pantothenate, and CoA biosynthesis. Univariate and multivariate statistical analysis showed that 9 metabolites had significant diagnostic value for CRC, among them, Guanosine with Area Under the Curve (AUC) values of 0.951 for the training group and0.998 for the validation group. Furthermore, analysis of four specific metabolites (N-Phenylacetylasparticacid, Tyrosyl-Gamma-glutamate, Tyr-Ser and Sphingosine) in serum samples of CRC patients before and after surgery indicated a return to healthy levels after an intervention. Our results suggest that serum metabolomics may be a valuable tool for the screening and monitoring of CRC patients.

Characterization of Thymoma by Ultra-Performance Liquid Chromatography—High Resolution Mass Spectrometry (UPLC-HRMS) and Metabolomics of Serum

Thymoma is a rare thymic tumor but is the most common anterior mediastinal tumor. Currently, there are still limitations regarding to its screening and the pathology remains elusive. In this study, nontargeted metabolomic analysis of serum was performed to study the metabolic characteristics of thymoma using ultra-performance liquid chromatography—high resolution mass spectrometry (UPLC-HRMS) in positive and negative ionization modes. The metabolites that were differentially abundant in thymoma were identified by MS/MS and matching to chemical standards. Forty-one metabolic features differentially abundant in thymoma were identified in the corresponding age groups, including uridine, dipeptides, arachidonic acid (AA)/8,11,14,17-eicosatetraenoic acid, lactic acid and its dimer, acylcarnitines, lysophosphatidylcholines (LPCs), and ceramide 1-phosphate (Cer1P) (d18:0/3:0). Among these metabolites, lactic acid and 9-decenoylcarnitine also had significant abundance changes between thymoma patients with and without myasthenia gravis (MG). Uridine, lactic acid and Cer1P (d18:0/3:0) may also be associated with the aberrant immune status in thymoma. Orthogonal partial least squares—discriminant analysis (oPLS-DA) showed that classification between thymoma and thymic hyperplasia was possible with 94.7% sensitivity, 100% specificity and 96.8% accuracy for all patient samples. The discriminant feature panel included uridine, AA/8,11,14,17-eicosatetraenoic acid, lactic acid dimer, and N-(1-deoxy-1-fructosyl)tryptophan. The distinct serum metabolic characteristics of thymoma identified in this study may offer insights into improvement of the diagnosis and discovery of new therapeutic strategies for thymoma, in addition to providing information for study of the underlying molecular mechanism of thymoma pathogenesis.

Biotransformation of white and black mustard grains through germination and enzymatic hydrolysis revealed important metabolites for antioxidant properties and cytotoxic activity against Caco-2 cells

Germination and enzymatic hydrolysis are biological processes with well-recognized positive effects on phenolic composition and antioxidant potential. This study aimed to apply those processes to white (Sinapsis alba) and black (Brassica nigra) mustard grains and to analyze the influences on the total phenolic content (TPC); phenolic and peptide profile determined by ultra-performance liquid chromatography–high resolution mass spectrometry (UPLC-HRMS); antioxidant potential (DPPH, ABTS, and FRAP assays); and cytotoxicity against Caco-2, a human colorectal adenocarcinoma cell line. Enzyme combinations for hydrolysis were different for each mustard grain, but for both species, enzymatic hydrolysis and germination showed a positive effect on antioxidant properties. From UPLC-HRMS analysis and molecular network studies, 14 peptides and 17 phenolic compounds were identified as metabolites released from mustard after processes application, which were strongly correlated with increased antioxidant activity. In addition, enzymatic hydrolysis applied in germinated mustard grains for both mustards increased the cytotoxic activity against Caco-2 human colorectal adenocarcinoma cell line.

Margaritaria nobilis L.f. (Phyllanthaceae) Ethanolic Extract: Low Acute Oral Toxicity and Antinociceptive Activity.

Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf's ethanolic extract is determined by ultra-performance liquid chromatography-high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals' consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.

Sulfated fucan could serve as a species marker of sea cucumber with endo-1,3-fucanase as the essential tool

In the past few decades, sulfated fucan from sea cucumber had attracted considerable interest owing to its abundant physiological activities. Nevertheless, its potential for species discrimination had not been investigated. Herein, particular attention was given to sea cucumber Apostichopus japonicus, Acaudina molpadioides, Holothuria hilla, Holothuria tubulosa, Isostichopus badionotus and Thelenota ananas to examine the feasibility of sulfated fucan as a species marker of sea cucumber. The enzymatic fingerprint suggested that sulfated fucan exhibited significant interspecific discrepancy and intraspecific stability, which revealed that sulfated fucan could serve as the species marker of sea cucumber, by utilizing the overexpressed endo-1,3-fucanase Fun168A and the ultra-performance liquid chromatography-high resolution mass spectrum. Moreover, oligosaccharide profile of sulfated fucan was determined. The oligosaccharide profile combined with hierarchical clustering analysis and principal components analysis further confirmed that sulfated fucan could serve as a marker with a satisfying performance. Besides, load factor analysis showed that the minor structure of sulfated fucan also contributed to the sea cucumber discrimination, besides the major structure. The overexpressed fucanase played an indispensable role in the discrimination, due to its specificity and high activity. The study would lead to a new strategy for species discrimination of sea cucumber based on sulfated fucan.

Role of Human Aldo-Keto Reductases in the Nitroreduction of 1-Nitropyrene and 1,8-Dinitropyrene.

1-Nitropyrene (1-NP) and 1,8-dinitropyrene (1,8-DNP) are diesel exhaust constituents and are classified by the International Agency for Research on Cancer as probable (Group 2A) or possible (Group 2B) human carcinogens. These nitroarenes undergo metabolic activation by nitroreduction to result in the formation of DNA adducts. Human aldo-keto reductases (AKRs) 1C1-1C3 catalyze the nitroreduction of 3-nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA), but the extent of AKR contribution toward the nitroreduction of additional nitroarenes, including 1-NP and 1,8-DNP, is currently unknown. In the present study, we investigated the ability of human recombinant AKRs to catalyze 1-NP and 1,8-DNP nitroreduction by measuring the formation of the respective six-electron reduced amine products in discontinuous ultraviolet-reverse phase high-performance liquid chromatography enzymatic assays. We found that AKR1C1-1C3 were able to catalyze the formation of 1-aminopyrene (1-AP) and 1-amino-8-nitropyrene (1,8-ANP) in our reactions with 1-NP and 1,8-DNP, respectively. We determined kinetic parameters (Km, kcat, and kcat/Km) and found that out of the three isoforms, AKR1C1 had the highest catalytic efficiency (kcat/Km) for 1-AP formation, whereas AKR1C3 had the highest catalytic efficiency for 1,8-ANP formation. Use of ultra-performance liquid chromatography high-resolution mass spectrometry verified amine product identity and provided evidence for the formation of nitroso- and hydroxylamino-intermediates in our reactions. Our study expands the role of AKR1C1-1C3, which are expressed in human lung cells, in the metabolic activation of nitroarenes that can lead to DNA adduct formation, mutation, and carcinogenesis.

Dual Effect of Tryptamine on Prostate Cancer Cell Growth Regulation: A Pilot Study.

Abnormal tryptophan metabolism is linked to cancer and neurodegenerative diseases, and tryptophan metabolites have been reported as potential prostate cancer (PCa) biomarkers. However, little is known about the bioactivities of tryptophan metabolites on PCa cell growth. In this study, MTT and transwell assays were used to study the cytotoxicities of 13 major tryptophan metabolites on PCa and normal prostate epithelial cell lines. Ultraperformance liquid chromatography–high resolution mass spectrometry (UPLC–HRMS) was used to analyze metabolic changes in cells treated with tryptamine. Flow cytometry, confocal imaging, and Western blot were used to test the apoptosis induced by tryptamine. It was shown that tryptamine had obvious inhibitory effects on PCa cell lines PC-3 and LNCaP, stronger than those on the normal prostate cell line RWPE-1. Tryptamine was further shown to induce apoptosis and inhibit PC-3 cell migration. Metabolic changes including amino acid metabolism related to cell proliferation and metastasis were found in PC-3 cells treated with tryptamine. Furthermore, a PC-3 xenograft mouse model was used to study the effect of tryptamine in vivo. The intratumoral injection of tryptamine was demonstrated to significantly reduce the tumor growth and tumor sizes in vivo; however, intraperitoneal treatment resulted in increased tumor growth. Such dual effects in vivo advanced our understanding of the bioactivity of tryptamine in regulating prostate tumor development, in addition to its major role as a neuromodulator.

Development of an analytical method to determine E7130 concentration in mouse plasma by micro-sampling using ultra-performance liquid chromatography–high resolution mass spectrometry

E7130 is a novel microtubule inhibitor and a promising tumor microenvironment ameliorator. Since the amount of the administration in preclinical study is very small due to the high potency of E7130, this study aimed to establish a sensitive analytical method to measure E7130 concentration in mouse plasma samples obtained via microsampling. A sensitive and validated method was developed based on ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC–HRMS). Chromatographic separation was achieved using a Waters ACQUITY UPLC BEH C18 1.7 µm (2.1 × 50 mm) column. Mobile phase A comprised 0.1% formic acid and 10 mM ammonium formate in water, and mobile phase B was methanol. A gradient elution was applied at a flow rate of 0.5 mL/min. The calibration curve drawn was linear in the 0.2–100 ng/mL E7130 concentration range for mouse plasma microsamples (10 µL). Analytical results demonstrated good precision (<6.7%) and accuracy (88.5%–100.0%) in E7130 quantitation, indicating that UHPLC–HRMS is a useful method for pharmacokinetic analysis and a valuable approach for the quantitation of hardly fragmented compounds.

Determination of Haloacetic Acids, Disinfection Byproducts, in Tap Water with Reversed-Phase Ultra-Performance Liquid Chromatography-High Resolution Mass Spectrometry

To establish a method for quantitative analysis of haloacetic acids (HAAs), disinfection byproducts, in tap water with reversed-phase ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry. Tap water samples were collected and 0.70 g/L ascorbic acid was added to eliminate residual chlorine. Then, the water samples were directly injected into the instrument for analysis after filtration. After separation on a pentafluorobenzene (PFP) column with an inner diameter of 1.0 mm at a higher linear velocity and a lower volume flow rate compared with those of a narrow-bore column, nine HAAs, namely, monochloroacetic acid (MCAA), monobromoacetic acid (MBAA), dichloroacetic acid (DCAA), bromochloroacetic acid (BCAA), dibromoacetic acid (DBAA), trichloroacetic acid (TCAA), bromodichloroacetic acid（BDCAA), chlorodibromoacetic acid (CDBAA) and tribromoacetic acid (TBAA), were examined by negative electrospray ionization and full MS/dd-MS 2 acquisition mode. In order to adjust for the matrix effect, matrix matching calibration curves were used to quantitate the nine HAAs. Good linearity was obtained for each of the nine HAAs within their respective linear ranges. The detection limits and quantification limits of the method were 0.020-1.0 μg/L and 0.060-3.0 μg/L. The recoveries were 69.8%-119%. The proposed method showed strengths in separation speed and qualitative accuracy. It did not require for complicated pretreatment procedures and can meet the need of tap water sample analysis.

Enantioselectivity and residue analysis of cycloxaprid and its metabolite in the pile and fermentation processing of Puer tea by ultraperformance liquid chromatography-high-resolution mass spectrometry.

The residues of cycloxaprid enantiomers and metabolites are investigated by ultraperformance liquid chromatography–high‐resolution mass spectrometry (UPLC‐HRMS) during raw and ripen Puer tea processing. A Chiralpak AG column with chiral stationary phase of amylose tris (3‐chloro‐5‐methylphenylcarbamate) is succeed to separate the 1R, 2S‐cycloxaprid, 1S, 2R‐cycloxaprid, and their metabolite, which is identified as nitrylene‐imidazolidine. It is not conversed 1R, 2S ‐cycloxaprid into 1S,2R‐cycloxaprid during Puer tea processing. The estimated half‐lives of the 1R,2S‐cycloxaprid and 1S,2R‐cycloxaprid are 0.97 and 1.1 h, respectively, and 1R,2S‐cycloxaprid decreases more quickly than the 1S,2R‐cycloxaprid. During raw Puer tea processing, the half‐lives of 1R, 2S‐cycloxaprid and 1S, 2R‐cycloxaprid are 1.68 h and 1.77 h, but the residue is still detected even if it is over 730 day. However, the half‐lives of 1R,2S ‐cycloxaprid and 1S,2R‐cycloxaprid are 0.60 day and 0.63 day during ripen tea processing. The amounts of metabolite are more in raw tea than in ripen tea; the terminal residues are still detected until 730 days during raw tea. A significant enantioselectivity of 1R, 2S‐cycloxaprid and 1S, 2R‐cycloxaprid is observed during raw tea or ripen tea processing. The degration result shows the enantioselectivity of cycloxaprid in raw or ripen Puer tea processing.

Rapid microwave synthesis of PCN-134-2D for singlet oxygen based-oxidative degradation of ranitidine under visible light: Mechanism and toxicity assessment

Two-dimensional porphyrin metal–organic frameworks (2D-PMOFs) showed potential applications in the field of photocatalysis. In this study, PCN-134-2D was rapidly prepared by the microwave-assisted solvothermal (MS) method for photocatalytic degradation of ranitidine (RAN), and exhibited enhanced photocatalytic performance due to the augmentation of the TCPP/BTB ratio (0.55). 93.1% of RAN could be effectively photodegraded in 120 min through PCN-134-2D under visible light. During the photosensitizing process, singlet oxygen (1O2) was proved to be the major reactive oxygen species (ROS) and showed the unique ability of non-radical resistance to conquer the inhibiting effects of inorganic anions (Cl−, HCO3−, NO3−, SO42−, H2PO4−) and natural organic matter (humic acid [HA]). The effects of practical reaction parameters were studied in detail. Light intensity and oxygen content were demonstrated as the key factors to photosensitization. The final removal rates of RAN in lake waters and river waters were 84.7% and 84.1% under the solar light. Meanwhile, the total organic carbon (TOC) removal rates were 30.4% and 31.5%, respectively. Ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was used to analyze the photodegradation products of the target RAN, and 17 intermediate compounds were obtained in ESI positive mode. The degradation pathways of RAN by 1O2 were proposed as C–N bond and C–S bond cleavage. Ecotoxicity assessment by the Ecological Structure Activity Relationships (ECOSAR) program indicated that most of the intermediate products were “not harmful” to fish, daphnid and green algae. The inhibition rate of Vibrio fischeri bioluminescence was approximately reduced 62% after RAN was treated by PCN-134-2D in 120 min.

A quantitative ultra-performance liquid chromatography high-resolution mass spectrometry analysis of steroids from human scalp hair

Hair steroid analysis offers the possibility to evaluate long-term steroid metabolism. It is especially beneficial when studying the steroid milieu in newborns and children, for example it can provide new insights into steroid metabolism over months and is unaffected by diurnal fluctuations in steroid concentrations. This study describes a quantitative and highly selective high-resolution mass spectrometry method for the simultaneous analysis of multiple steroids from human scalp hair. The developed method utilizes parallel reaction monitoring in the analysis of hydroxylamine derivatized steroids from hair samples first washed with isopropanol, extracted with methanol, and further purified with solid-phase extraction and liquid-liquid extraction. The method was proven suitable for the quantitative analysis of endogenous glucocorticoids (cortisol [1.5–364 pg/mg]; cortisone [3.6–355 pg/mg]; corticosterone [0.7–347 pg/mg]; 11-deoxycortisol [0.1–343 pg/mg]), androgens (testosterone [0.1–288 pg/mg]; dehydroepiandrosterone [0.3–288 pg/mg]; androstenedione [0.1–285 pg/mg]; 11β-hydroxyandrostenedione [0.3–304 pg/mg]), progestogens (pregnenolone [0.1–313 pg/mg]; progesterone [0.1–313 pg/mg]; 17α-hydroxypregnenolone [0.3–315 pg/mg]; 17α-hydroxyprogesterone [0.7–330 pg/mg]; 21-hydroxyprogesterone [0.6–320 pg/mg]), and estrogens (estrone [0.1–267 pg/mg]; estradiol [0.5–274 pg/mg]). In addition, 11-ketoandrostenedione [0.6–60 pg/mg]; dihydrotestosterone [0.3–290 pg/mg]; 11-ketotestosterone [0.1–12 pg/mg]; and 5α-androstanedione [0.6–281 pg/mg] could be analyzed semi-quantitatively. Aldosterone [3.5–346 pg/mg]; 11β-hydroxytestosterone [0.3–300 pg/mg]; and 11-ketodihydrotestosterone [0.3–300 pg/mg] were also included in the method, but their concentrations were below the lower limit of quantification in all tested hair samples. The method was applied for the analysis of authentic hair samples from different age groups ranging from newborns to adults, including mothers within 48 h after delivery. The newborn hair samples displayed the widest variety and had also the highest amounts of steroids in comparison to the samples of the other groups.