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The potential of the green macroalga Ulva lactuca is increasingly recognized, not only for its environmental benefits, but also for its applications in various industries, including food, pharmaceuticals, and cosmetics. Given this insight, a comprehensive analysis of the chemical profile of U. lactuca from the Adriatic Sea was carried out. The hydrodistillate, rich in (Z,Z,Z)-hexadeca-7,10,13-trienal and hexadecanoic acid, underlines its importance for health-related uses, particularly in lipid metabolism and cellular integrity. Fatty acid analysis showed a predominance of palmitic acid and a favorable n-6/n-3 polyunsaturated fatty acid ratio, suggesting that U. lactuca can make a valuable contribution to a balanced diet. In addition, essential amino acids, including leucine, valine, and isoleucine, support its use as a functional ingredient for muscle repair and metabolic health. The ethanol extract contained 56 compounds, including derivatives of fatty acids, phenolic acids, pigments, flavonoids, and steroids. Many of them, such as hexadecasphinganine, azelaic acid, 5-sulfosalicylic acid, and pheophytin a, have proven roles or potentials in promoting human health. These results confirm that U. lactuca is a rich source of bioactive compounds, emphasizing its potential in scientific research and its expanding industrial applications in health, nutrition, and cosmetics. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the inhibitory effects of Plantago asiatica L. on DPP-4 and to determine the active compounds responsible for this inhibition. Extracts were prepared from the root and aerial portions of the plant using various polar solvents. The DPP-4 inhibition of these extracts was analyzed in an extracellular assay and then assigned to either the high or low inhibition group. The chemical profiles of these extracts were analyzed using an LC-MS method. The ion fragments that were potent in the high inhibition extracts were selected through OPLS-DA and correlation analysis, and then identified and obtained for verification of DPP-4 inhibition in both the extracellular assay and the Caco-2 cell line. The extracts showed various inhibitory activities with an average inhibition of 28.4 %. A total of 20 compounds were selected from the extracts with higher inhibitory activity and identified. Six of them, baicalein, scutellarein, calceolarioside B, isoacteoside, verbascoside, and plantamajoside, exhibited DPP-4 inhibition with IC 50 values of 44.32, 59.90, 112.71, 157.02, 154.58, and 195.07 μg/mL, respectively, in extracellular assays. They also showed inhibition of DPP-4 on the Caco-2 cell line, with IC 50 values of 31.56, 34.71, 20.29, 33.29, 24.52, and 87.88 μg/mL, respectively. The extracts from PAL showed inhibitory activity towards DPP-4, and the related compounds were identified and verified. [Display omitted] • Plantago asiatica L. was shown to have inhibitory activity against DPP-4 based on the evidence provided. • Active chemicals were screened and identified by comparing the chemical profiles of high and low activity extracts. • The activity of six compounds was confirmed on both extracellular and Caco-2 cell line tests with their IC 50. [ABSTRACT FROM AUTHOR]

Abstract Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI. [ABSTRACT FROM AUTHOR]

Introduction: Liuweizhiji Gegen‐Sangshen (LGS) oral liquid is a Chinese patent medicine that is widely used for the prevention and treatment of alcoholic liver disease in clinical practice. However, the chemical complexity of LGS has not yet been investigated. Objective: The aim of this study was to rapidly identify chemical constituents of LGS and establish a quality control method based on fingerprint and quantitative analysis. Methodology: A comprehensive strategy was used by combining qualitative analysis by ultra‐performance liquid chromatography tandem quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) and fingerprint analysis by high‐performance liquid chromatography with diode array detection (HPLC‐DAD). Results: A total of 162 chemical components in LGS, including 91 flavonoids, 31 organic acids, and 20 phenolic compounds, were identified or preliminarily characterized in both positive and negative ion modes based on the UPLC‐Q‐TOF‐MS results. Of these, 37 were confirmed with the reference standards. In fingerprint analysis, 23 peaks were chosen as common peaks and used to evaluate the similarity of different batches of LGS. Subsequently, a rapid quantification method was optimized and validated for the simultaneous determination of multiple chemical markers in LGS. The validated quantitative method was successfully used to analyze different batches of LGS samples. Conclusion: The proposed comprehensive strategy combining HPLC‐DAD fingerprinting and multi‐component quantification demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be used as a reference for the overall quality consistency evaluation of Chinese patent medicines. In this study, a comprehensive strategy combining ultra‐performance liquid chromatography tandem quadrupole time‐of‐flight mass spectrometry qualitative analysis and high‐performance liquid chromatography diode array detector fingerprinting analysis was used for a rapid, efficient and sensitive quality control of Liuweizhiji Gegen‐Sangshen oral liquid. [ABSTRACT FROM AUTHOR]

The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver microsomes (HLM) to mimic phase I metabolism reactions for the first time. Employing a combination of an HLM assay and UHPLC-HRMS analysis enabled the identification of seven metabolites of miconazole, undescribed so far. Throughout the incubation with HLM, miconazole underwent biotransformation reactions including hydroxylation of the benzene ring and oxidation of the imidazole moiety, along with its subsequent degradation. Additionally, based on the obtained results, screen-printed electrodes (SPEs) were optimized to simulate the same biotransformation reactions, by the use of a simple, fast, and cheap electrochemical method. The potential toxicity of the identified metabolites was assessed using various in silico models. [ABSTRACT FROM AUTHOR]

An intelligent wine detection and traceability method based on infrared spec-troscopy and machine learning is proposed, in order to meet the needs of online rapid nondestructive testing of wine. On the basis of extracting infrared spectrum of wine, the principal component analysis (PCA) – support vector machine (SVM) model was modified by chemometrics. A total of 300 grape wine samples were collected from six production areas. The composition of the samples was analyzed by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). According to the experimental results, indole, sulfacetamide and caffeine were selected as characteristics of different origins. Near infrared spectral wavelengths of wine samples were compressed between 900 and 2,500 nm. The ranges of 1,000 nm ~ 1,400 nm and 1,500 nm ~ 1800 nm were selected for PCA principal component analysis and key spectral wavelengths were extracted. The unsupervised learning model of SVM is used to classify and identify key spectral wavelengths. The experimental results show that the algorithm has higher classification accuracy than traditional PCA-LDA, PCA and other algorithms. The classification accuracy of the algorithm is improved from 98.3 to 99.75%. The improved PCA-SVM algorithm can achieve fast and loss-less source tracing of wine.

Introduction and objective: Taking into consideration the challenges of lipid analytics, present study aims to design the best high-throughput workflow for detection and annotation of lipids. Material and methods: Serum lipid profiling was performed on CSH-C18 and EVO-C18 columns using UHPLC Q-TOF-MS and generated lipid features were annotated based on m/z and fragment ion using different software. Result and discussion: Better detection of features was observed in CSH-C18 than EVO-C18 with enhanced resolution except for Glycerolipids (triacylglycerols) and Sphingolipids (sphingomyelin). Conclusion: The study revealed an optimized untargeted Lipidomics-workflow with comprehensive lipid profiling (CSH-C18 column) and confirmatory annotation (LipidBlast). [ABSTRACT FROM AUTHOR]

In this study, nine forced degradation products of maraviroc were found using chemometric analysis. This antiretroviral drug was subjected to photolytic, oxidative, as well as neutral, basic and acidic hydrolysis stress conditions. Additionally, its electrochemical transformation on platinum, gold and glassy carbon screen-printed electrodes was examined. This study showed that maraviroc is especially susceptible to UVA, H2O2 and electrochemical degradation, while being resistant to neutral and acidic hydrolysis. A cluster analysis showed that the electrochemical transformation, with particular reference to the platinum electrode, is able to partially simulate the forced degradation processes, especially in the context of redox reactions. These findings indicate that the electrochemical methods can be considered as quick and relatively low-cost supplements to the commonly applied forced degradation procedures. [ABSTRACT FROM AUTHOR]

In recent years, metabolomics has emerged as a pivotal approach for the holistic analysis of metabolites in biological systems. The rapid progress in analytical equipment, coupled to the rise of powerful data processing tools, now provides unprecedented opportunities to deepen our understanding of the relationships between biochemical processes and physiological or phenotypic conditions in living organisms. However, to obtain unbiased data coverage of hundreds or thousands of metabolites remains a challenging task. Among the panel of available analytical methods, targeted and untargeted mass spectrometry approaches are among the most commonly used. While targeted metabolomics usually relies on multiple‐reaction monitoring acquisition, untargeted metabolomics use either data‐independent acquisition (DIA) or data‐dependent acquisition (DDA) methods. Unlike DIA, DDA offers the possibility to get real, selective MS/MS spectra and thus to improve metabolite assignment when performing untargeted metabolomics. Yet, DDA settings are more complex to establish than DIA settings, and as a result, DDA is more prone to errors in method development and application. Here, we present a tutorial which provides guidelines on how to optimize the technical parameters essential for proper DDA experiments in metabolomics applications. This tutorial is organized as a series of rules describing the impact of the different parameters on data acquisition and data quality. It is primarily intended to metabolomics users and mass spectrometrists that wish to acquire both theoretical background and practical tips for developing effective DDA methods. [ABSTRACT FROM AUTHOR]

• A novel strategy was proposed for the comprehensive analysis of Magnolia officinalis. • A total of 103 compounds were identified from the whole plant of Magnolia officinalis. • Multidimensional chemical-biological analysis of Magnolia officinalis was established. • The 6 parts of Magnolia officinalis were explored and compared for the first time. • Magnolol and honokiol were found to be synergistic α-glucosidase inhibitors. Magnolia bark is a traditional Chinese medicine used for hypoglycaemia. With the widespread use of Magnolia bark, its resources are facing a serious shortage. To address this issue, a strategy based on high-coverage mass spectrometry (HCMS) and multidimensional chemical-biological analysis (MCBA) was proposed for the comprehensive exploration of Magnolia officinalis which is the main source of Magnolia bark. The strategy is divided into three main steps. In the first step, the stem bark, stem xylem, root bark, root xylem, leaf and rootlet of Magnolia officinalis were comprehensively analyzed using high-coverage mass spectrometry. In the second step, multivariate statistical analysis was used to explore the heterogeneity of the six parts and detect differential chemical components. In the third step, a combination of experimental screening and molecular docking was used to explore α-glucosidase inhibitors from Magnolia officinalis. Multidimensional chemical-biological analysis (MCBA) of Magnolia officinalis was achieved by combining the last two steps. Finally, a total of 103 compounds were identified from the whole plant of Magnolia officinalis. Differential components of stem bark, stem xylem, leaf, root bark, root xylem and rootlet were systematically revealed. A pair of positional isomers, namely magnolol and honokiol, were found to be α-glucosidase inhibitors. The activity of their combination is superior to that of each single compound, indicating that magnolol and honokiol are in a synergistic relationship. This strategy contributes to comprehensive exploitation of functional plants and effective alleviation of resource shortage. This study also provides a research paradigm for other similar traditional Chinese medicinal plants. [ABSTRACT FROM AUTHOR]

In the face of mounting global antibiotic resistance, which has become a critical clinical problem, antimicrobial peptides (AMPs) have received considerable interest as new therapeutics with the efficacy for the treatment of multidrug-resistant (MDR) infections due to their novel mechanism. However, certain inherent shortcomings such as instability seriously limit their systemic applications in the clinic. In this study, we intend to clarify the connection between three configurations of IK8 and their stability in plasma and liver S9 of various species by confirming the metabolites. The structural information of these metabolites was scanned and identified using HPLC and Q-TOF, respectively. The results found that IK8-D exhibits superior stability, compared with IK8-2D and IK8-L in plasma and liver S9 incubation, which indicated D- type amino acids could significantly increase the stability of antimicrobial peptides. [ABSTRACT FROM AUTHOR]

Pigeonpea (Cajanus cajan) is an important crop in semi-arid regions and a significant source of dietary proteins in India. The plant is sensitive to salinity stress, which adversely affects its productivity. Based on the dosage-dependent influence of salinity stress on the growth and ion contents in the young seedlings of pigeonpea, a comparative proteome analysis of control and salt stressed (150 mM NaCl) plants was conducted using 7 days-old seedlings. Among various amino acids, serine, aspartate and asparagine were the amino acids that showed increment in the root, whereas serine, aspartate and phenylalanine showed an upward trend in shoots under salt stress. Furthermore, a label-free and gel-free comparative Q-Tof, Liquid Chromatography-Mass spectrometry (LC–MS) revealed total of 118 differentially abundant proteins in roots and shoots with and without salt stress conditions. Proteins related to DNA-binding with one finger (Dof) transcription factor family and glycine betaine (GB) biosynthesis were differentially expressed in the shoot and root of the salinity-stressed seedlings. Exogenous application of choline on GB accumulation under salt stress showed the increase of GB pathway in C. cajan. Gene expression analysis for differentially abundant proteins revealed the higher induction of ethanolamine kinase (CcEthKin), choline-phosphate cytidylyltransferase 1-like (CcChoPh), serine hydroxymethyltransferase (CcSHMT) and Dof protein (CcDof29). The results indicate the importance of, choline precursor, serine biosynthetic pathways and glycine betaine synthesis in salinity stress tolerance. The glycine betaine protects plant from cellular damages and acts as osmoticum under stress condition. Protein interaction network (PIN) analysis demonstrated that 61% of the differentially expressed proteins exhibited positive interactions and 10% of them formed the center of the PIN. Further, The PIN analysis also highlighted the potential roles of the cytochrome c oxidases in sensing and signaling cascades governing salinity stress responses in pigeonpea. [ABSTRACT FROM AUTHOR]

A polyphenol-rich extract with an expressive vasodilator effect was obtained from fresh leaves of Alpinia zerumbet (AZ), a medicinal plant. The vasodilator effects of AZ from different extraction conditions were studied in the perfused mesenteric vascular bed, and total polyphenol content (TPC) was determined for all samples. UHPLC/ESI-QTOF-MS analysis established the chemical composition of AZ extracts, and a molecular network from GNPS (Global Natural Products Social Molecular Networking) generated a list of putative compounds. Briefly, results show a 50% hydroethanolic extract from fresh leaves (AZE4) as the best extraction condition, presenting the greatest vasodilator effect (ED50 = 7.1 ± 1.7 µg) and TPC (16.30 mg GAE/g ± 0.44). Flavonoids are the main constituents and alpinetin, kaempferol-3-O-glucuronide, (−)-epicatechin, and pinocembrin were identified as major compounds. The least effective extraction condition was 50% hydroethanolic extract from dried leaves without heating. This extract showed the smallest vasodilator response (ED50 = 29.1 ± 4.3 µg) and TPC (6.35 mg GAE/g ± 0.08), reinforcing the use of fresh leaves and heating step to improve extracts performance. The vasodilator effect and the main flavonoid composition of AZE4 provide experimental support, suggesting this extract as a potential source of bioactive flavonoids to treat cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Sugar phosphates are important intermediates of central carbon metabolism in biological systems, with roles in glycolysis, the pentose–phosphate pathway, tricarboxylic acid (TCA) cycle, and many other biosynthesis pathways. Understanding central carbon metabolism requires a simple, robust and comprehensive analytical method. However, sugar phosphates are notoriously difficult to analyze by traditional reversed phase liquid chromatography. Results Here, we show a two-step derivatization of sugar phosphates by methoxylamine and propionic acid anhydride after chloroform/methanol (3:7) extraction from Populus leaf and developing wood that improves separation, identification and quantification of sugar phosphates by ultra high performance liquid chromatography–electrospray ionization–mass spectrometry (UHPLC–ESI–MS). Standard curves of authentic sugar phosphates were generated for concentrations from pg to ng/μl with a correlation coefficient R 2 > 0.99. The method showed high sensitivity and repeatability with relative standard deviation (RSD)

YE (yeast extract) has been widely used in the flavor industry as the source to produce the high-quality meaty and umami flavors. It is because YE is rich in the savory and mellow constituents and is important precursors to generate aromas via thermal treatment. This study aims to investigate the change of meaty aroma and umami taste in the hydrolyzed YE during the thermal treatment. In this study, gas chromatography–olfactometry-mass spectrometer (GC-O-MS) was employed to detect the aroma-active compounds, and systematic approaches was used for the taste-active umami proteolytics separation and detection. The reaction conditions of two optimal samples, YE-A and YE-B, were as follows: the reaction time (A) was 90 min, the reaction temperature (B) was at 115 °C, the concentration of YE solution (C) was 0.4 g/mL, and pH (D) was 5.5 and 6.0, respectively. The GC-O-MS results show YE-A contains 31 and YE-B contains 29 key aroma-active compounds, and the priorities of four factors are both C > B > D > A. The key aroma-active compounds that contributed to meaty flavor were both 3-(methylthio)propanal (cooked potato-like), dihydro-5-pentyl-2(3H)-furanone (coconut-like, peach-like), 2-ethyl-3,5-dimethyl pyrazine (potato-like) etc. with OAVs greater than 1. The Q-TOF–MS/MS results show that YE-A contained five umami peptides, which were Ala-Asp-Ala, Pro-Gly-Asp, Glu-Met-His, Gln-Pro-Ser and Val-Glu-His; whereas YE-B contained four umami peptides, which were Glu-Asp, Pro-Ser-Gly, Ala-Glu-Ala, and Gly-Gly-Pro-Gly. [ABSTRACT FROM AUTHOR]

The influence of ionizing radiation on the physicochemical properties of panipenem in the solid-state was studied. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile panipenem. Spectroscopic (FT-IR, Raman), chromatography (HPLC and HPLC-MS) and X-ray powder diffraction (XRPD) studies have shown that irradiation of panipenem with the 25 kGy, the dose required to achieve sterility, does not change the physicochemical properties of the studied compound. The antimicrobial activity of panipenem irradiated with the dose of 25 kGy was reduced for three species. It was confirmed that the decrease in antimicrobial activity might be related to the isomerization of panipenem. [ABSTRACT FROM AUTHOR]

In the face of mounting global antibiotic resistance, which has become a critical clinical problem, antimicrobial peptides (AMPs) have received considerable interest as new therapeutics with the efficacy for the treatment of multidrug-resistant (MDR) infections due to their novel mechanism. However, certain inherent shortcomings such as instability seriously limit their systemic applications in the clinic. In this study, we intend to clarify the connection between three configurations of IK8 and their stability in plasma and liver S9 of various species by confirming the metabolites. The structural information of these metabolites was scanned and identified using HPLC and Q-TOF, respectively. The results found that IK8-D exhibits superior stability, compared with IK8-2D and IK8-L in plasma and liver S9 incubation, which indicated D- type amino acids could significantly increase the stability of antimicrobial peptides.

Abstract Background Toddalia asiatica root bark as an effective hemostatic natural medicine or Chinese materia medica was applied in China for long history, its complex drug action mechanisms and unclear substance basis have been constraining the development of this drug. Results An intelligentized strategy by LC-ESI Q-TOF MSE was presented in this study for rapid identification of hemostatic chemical constituents from this natural medicine. Chromatographic separation was performed on a C18 column (150 mm × 2.1 mm, 1.8 μm), the MSE data in both negative and positive ion modes were acquired to record the high-accuracy MS and MS/MS data of all precursor ions. To reduce the false positive identifications, structural confirmation was conducted by comparison with the isolated reference standards (tR and MS, MS/MS data) or matching with natural product databases. Bioassay-guided fractionation of the extract of T. asiatica root bark was also carried out. Conclusions As a consequence, 31 natural compounds in T. asiatica root bark got putatively characterized. There were four main coumarins, isopimpinellin (Cp.23), pimpinellin (Cp.24), coumurrayin (Cp.30) and phellopterin (Cp.34) isolated and identified from T. asiatica root bark. The present study provided candidate strategy that helps to effectively identify the primary natural compounds of TCM or other complex natural medicines, and then promote development and application of natural medicines and their medicinal resources.

A procedure was established and fully validated for the screening and quantification of fourteen synthetic antidiabetic adulterants in herbal pharmaceuticals and health foods, including metformin (MF), buformin (BF), phenformin (PHF), rosiglitazone (RGZ), pioglitazone (PGZ), chlorpropamide (CPM), glipizide (GPZ), tolbutamide (TBM), gliclazide (GCZ), glibenclamide (GBM), glimepiride (GMR), repaglinide (RGN), gliquidone (GQD) and nateglinide (NGN). The samples were extracted by methanol and separated by HPLC. Retention times and ultraviolet spectra were used for the preliminary screening, and the suspected adulterants were then confirmed by liquid chromatography-quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS/MS) and quantified by HPLC. The developed procedure was successfully applied to assess twenty-four herbal samples, and PHF, GCZ, GBM, MF, GPZ and BF were found in many. To the best of our knowledge, this is the first report of simultaneous screening and quantification of these fourteen synthetic antidiabetic adulterants from any matrix. [ABSTRACT FROM AUTHOR]

Baby bottles made of polypropylene, Tritan® and silicone were evaluated regarding the migration of non-volatile compounds using UPLC-QTOF-MS. Twenty-seven compounds were identified. In all polypropylene samples the migration of 2.2′-(tridecylimino)bis-ethanol and derivatives thereof were detected in concentrations below the specific migration limit (1.2 mg.kg−1). Furthermore, clarifying agents and glycerol derivatives were detected. Tritan baby bottle showed the migration of one slip additive. On the other hand, twenty compounds were detected in silicone baby bottles. Most of them were unknown compounds derived from acrylates. Once the migrants were identified, the risk assessment was carried out using the Threshold of Toxicological Concern (TTC) approach. The risk assessment of migrants coming from silicone samples showed levels above the threshold recommended as safe for babies. Unlabelled Image • Baby bottles made of polypropylene, Tritan, and silicone were studied. • Twenty-seven migrants were identified using UPLC-QTOF-MS. • Intentionally added substances were identified in polypropylene baby bottles. • Cure additives were detected coming from silicone baby bottle. • Risk assessment showed levels above the threshold recommended by Cramer. [ABSTRACT FROM AUTHOR]

The influence of ionizing radiation on the physicochemical properties of betamipron in solid-state was studied. No changes for betamipron irradiated with a dose of 25 kGy, required to attain sterility, was observed by spectroscopic and chromatographic methods. Solid betamipron has proven to be very stable on irradiation, and irradiation has been found to be a suitable method for its sterilization. [ABSTRACT FROM AUTHOR]

One of the best sterilization methods for chemically unstable drugs, such as carbapenems, is irradiation. The chemical and physical properties of radiosterilized imipenem and cilastatin were analyzed using spectrophotometric and chromatographic methods. Unstable free radicals were presented in samples after irradiation; their mean lifetime was 142 ± 64 h. The antibacterial activity of cefozopran hydrochloride irradiated with a dose of 25 kGy changed for Klebsiella pneumoniae and Escherichia coli. Imipenem and cilastatin in the solid state are not resistant to radiation sterilization; therefore, this method cannot be used for sterilization of this compound. [ABSTRACT FROM AUTHOR]

Photostability of an antidepressant agomelatine under the simulated solar radiation was studied. Quantitative and qualitative analysis of this process was performed with the use of UHPLC-DAD system coupled with a high resolution hybrid ESI-Q-TOF mass spectrometer. In contrast to the foregoing studies agomelatine turned out to be relatively photolabile compound. During the experiment six transformation products were formed, and their structures were elucidated on the basis of MS/MS fragmentation spectra. Four of these photoproducts were found to be a result of aromatic and aliphatic hydroxylation. Additionally, identified products were submitted to the in silico toxicity evaluation, which showed that some of them could be more mutagenic or toxic to rodents than the parent compound. [ABSTRACT FROM AUTHOR]

High-resolution mass spectrometry (HRMS) in full scan mode acquires all ions present in the sample of interest offering a lot of qualitative information. This, in combination with the improved performance of the new generation HRMS systems, triggers more (bio) analysts to switch from triple quad MS systems to HRMS for quantitative analysis. Quantitative processing of HRMS data is performed based on narrow mass extraction windows rather than on nominal mass product ion chromatograms (SRM or MRM). Optimal processing of HRMS data requires different considerations and software tools and can have an impact on data processing and final results. The selection of centroid versus continuum/profile data for processing, selection of the optimal narrow mass extraction window, using theoretical versus measured accurate mass for the extraction of the ion chromatograms as well as differences in calculations and data handling residing in the different vendor software packages are tackled in the presented manuscript. These differences are illustrated on HRMS data acquired for the same plasma samples on three different platforms, i.e., a Sciex QToF, a Waters QToF, and a Thermo Orbitrap system, and processed in four different software packages, i.e., Sciex Analyst® TF, Waters Masslynx, Waters Unifi, and Thermo Xcalibur. The impact of these differences on quantitative HRMS performance was evaluated on calibration curves of eight small molecule compounds in plasma using four different ways of processing. Simple guidelines are provided for the selection of an optimal mass extraction window for continuum and centroided data.Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: The radiation sterilization is one of the best methods for sterilizing vulnerable degradation drugs like cefozopran hydrochloride. Results: Chemical stability of radiosterylized cefozopran hydrochloride, was confirmed by spectrophotometric and chromatographic methods. EPR studies showed that radiation has created some radical defects whose concentration was no more than several dozen ppm. The antibacterial activity of cefozopran hydrochloride irradiated with a dose of 25 kGy was unaltered for Gram-positive bacteria but changed for two Gram-negative strains. The radiation sterilized cefozopran hydrochloride was not in vitro cytotoxic against human CCD39Lu normal lung fibroblast cell line. Conclusions: Cefozopran hydrochloride in solid state is not resistant to radiation sterilization and this method cannot be used for sterilization of this compound.

Ciguatera poisoning (CP) is a common seafood intoxication mainly caused by the consumption of fish contaminated by ciguatoxins. Recent studies showed that Caribbean ciguatoxin-1 (C-CTX1) is the main toxin causing CP through fish caught in the Northeast Atlantic, e.g., Canary Islands (Spain) and Madeira (Portugal). The use of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) combined with neuroblastoma cell assay (N2a) allowed the initial confirmation of the presence of C-CTX1 in contaminated fish samples from the abovementioned areas, nevertheless the lack of commercially available reference materials for these particular ciguatoxin (CTX) analogues has been a major limitation to progress research. The EuroCigua project allowed the preparation of C-CTX1 laboratory reference material (LRM) from fish species (Seriola fasciata) from the Madeira archipelago (Portugal). This reference material was used to implement a liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) for the detection of C-CTX1, acquisition of full-scan as well as collision-induced mass spectra of this particular analogue. Fragmentation pathways were proposed based on fragments obtained. The optimized LC-HRMS method was then applied to confirm C-CTX1 in fish (Bodianus scrofa) caught in the Selvagens Islands (Portugal).

Highlights • Isolation of bioactive stilbenes. • Identification and quantification of stilbenes by Q-TOF system. • Evaluation of matrix effect. • Comparison of stilbene content in different vegetative parts of grape. Abstract A combined extract from three different interspecific grape crosses was used for the isolation of bioactive stilbenes. High-performance liquid chromatography coupled to hybrid quadrupole time-of-flight (Q-TOF) mass spectrometry was employed for the identification and determination of the analytes. A total of 27 stilbene derivatives were identified with mass accuracy ranging from −1.18 to 3.41 ppm. A subset of 16 compounds (cis/trans -piceid, cis/trans -piceatannol, cis/trans -resveratrol, cis/trans -scirpusin A, cis/trans -ε-viniferin, cis/trans -ω-viniferin, cis/trans - δ -viniferin, and E/Z -miyabenol C) were quantified and compared in the grape stems, seeds, skins, and juice from three different interspecific crosses. The stems and skins were the richest and second richest sources for all targeted stilbenes, respectively. The only compounds found in considerable amounts in grape juice were cis - and trans -piceids. The performance of unit resolution tandem mass spectrometric QqQ system was compared to the Q-TOF mass spectrometer in terms of matrix effects. The detection by QqQ unexpectedly exhibited an elevated matrix effect with a high degree of ion enhancement, especially in samples of grape stems and skins, while the Q-TOF system showed notably lower matrix effects. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New metabolites of vardenafil were found and their chemical structures were elucidated. • The complete hepatic metabolism pathway of vardenafil was proposed. • Chemometric method was used for multivariate comparison of photocatalytic and HLM biological metabolic LC-ESI-HRMS profiles. • For the first time WO 3 catalyst was used for simulation of drug metabolism process. • A heterogeneous WO 3 photocatalysis was found to be a complementary method for mimicking phase I metabolism reactions. Abstract The in vitro metabolism of vardenafil, a selective phosphodiesteraze type 5 (PDE-5) inhibitor was investigated with the use of biological HLM method in comparison to TiO 2 and WO 3 assisted photocatalytic approach. The main objective of this study was to identify the transformation routes and elucidate metabolite structures. The samples were analyzed by LC-ESI-HRMS system to obtain metabolism pathways and confirm the structures of new metabolites. Deethylated vardenafil was identified as a main transformation product and additionally, nine new, not yet described, metabolites were found in HLM samples. The photocatalytic process with the use of TiO 2 and WO 3 allowed to observe five and seven transformation products respectively. The multivariate chemometric comparison of the obtained results shows WO 3 assisted photocatalysis as a more suitable approach of phase I metabolism simulation method. [ABSTRACT FROM AUTHOR]

Abstract: In this study the comparison of human liver microsomes in in vitro incubation as well as ZnO‐ and TiO2‐assisted photocatalytic degradation of clozapine as a mimicking method of phase I metabolism transformation was performed. Based on reversed‐phase UHPLC separation and high‐resolution MS/MS data, eight transformation products were identified and seven of them were found to be hepatic metabolites of the parent compound. The multivariate chemometric comparison of the obtained results shows ZnO‐assisted photocatalysis to be a more suitable approach to phase I metabolism simulation. The photocatalytic experiments demonstrated that the disappearance of clozapine followed pseudo‐zero order kinetics. [ABSTRACT FROM AUTHOR]

Polymeric tannins from grapes have always been reported as an unresolved broad peak in HPLC chromatograms, and this has severely limited their identification to date. This study aimed to disassemble this broad peak and explore the polymeric tannin molecules inside. By applying centrifugal partition chromatography (CPC), an efficient separation approach was developed to split the broad peak of grape seed tannins into fractions. Then, the fractions were analyzed by Q-ToF (quadrupole time-of-flight mass spectrometry) to determine the corresponding structures of the tannins. The results suggest that grape seed polymeric tannins were eluted consecutively according to their degree of polymerization (DP). Condensed tannins identified in wine grape seed have a range of DP and degree of galloylation (DG) up to 20 and 11, respectively. The molecular mass of the largest molecule detected was 6067. To our knowledge, this is the first report to offer an insight into the broad peak of polymeric tannins found with HPLC and to characterize the tannins with a DP up to 20 as shown by HRMS and MS/MS data. [ABSTRACT FROM AUTHOR]

This paper presents a rapid, sensitive and precise method for the determination of metaldehyde in human blood, using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Separation was performed with a Poroshell 120 EC-C18 column; 2.7 μm atrazine‑d5 (IS) and 200 mg NaCl were added to the blood sample. Proteins in human blood were precipitated using acetonitrile; the supernatant was then analyzed with the UHPLC-Q-TOF-MS or HPLC-QqQ-MS/MS system. The results of selectivity, linearity, accuracy, precision, limits of quantification, recovery, and matrix effects were sufficient to enable the measurement of metaldehyde in human blood samples. In addition, we proposed a fragmentation pathway involving ammonium adduct fragment ions for metaldehyde. [ABSTRACT FROM AUTHOR]

Forced degradation of toloxatone in solutions under basic, acidic, neutral, photo UV–VIS, photo UVC and oxidative stress conditions was investigated and structural elucidation of its degradation products was performed with the use of UHPLC system coupled ESI-Q-TOF mass spectrometer. Eight degradation products were found and their masses and formulas were obtained with high accuracy (0.09–3.79 ppm). The structure of unknown degradation products were elucidated from MS/MS fragmentation spectra of all analyzed compounds. Additionally, whole signals of decomposed substances were compared chemometrically. It was found that toloxatone is fragile towards basic hydrolysis, oxidative conditions and UVC irradiation. Finally, the toxicity of transformation products was computationally evaluated and compared in multivariate manner. [ABSTRACT FROM AUTHOR]

Clinical metabolomics studies often have to cope with limited sample amounts, thus miniaturized liquid chromatography (LC) systems are a promising alternative. Their applicability has already been demonstrated in various fields, including a few metabolomics studies that mainly used reversed-phase chromatography. However, hydrophilic interaction chromatography (HILIC), which is widely used in metabolomics due to its particular suitability for the analysis of polar molecules, has rarely been tested for miniaturized LC-MS analysis of small molecules. In the present work, the suitability of a capillary HILIC (CapHILIC)-QTOF-MS system for non-targeted metabolomics was evaluated based on extracts of porcine formalin-fixed, paraffin-embedded (FFPE) tissue samples. The performance was assessed with respect to the number and retention time span of metabolic features as well as the analytical repeatability, the signal-to-noise ratio and the signal intensity of 16 annotated metabolites from different compound classes. The results were compared with a well established narrow-bore HILIC-QTOF-MS system. Both platforms have detected a similar number of features and performed excellent with respect to retention time stability (median RT span <0.05 min) and analytical repeatability (>75% of features with CV < 20%). The signal areas of all metabolites assessed were increased up to 18-fold by the use of CapHILIC, although the signal-to-noise ratio was only improved for 50% of the metabolites. An even better reproducibility (median CV = 5.2%) and up to 80-fold increase in signal intensity were observed after optimization of CapHILIC conditions for analysis of bile acid standard solutions. Even though the observed improvement for specific bile acids (e.g. taurocholic acid) in biological matrix needs to be evaluated, the platform comparison indicates, that the tested CapHILIC system is particularly suitable for analyses of a less broad metabolite spectrum, and specifically optimized chromatography. [Display omitted] • Comparable analytical performance of CapHILIC-QTOF-MS to narrow-bore HILIC QTOF-MS. • The extent of improvement in signal intensity and sensitivity varies by metabolite class. • Up to 79-fold increase in signal intensity for reference substances (bile acids) using CapHILIC [ABSTRACT FROM AUTHOR]

Ultra high performance liquid chromatography (UHPLC), coupled with accurate quadrupole-time-of-flight (Q-TOF) mass spectrometry, was used for the stability study of acetylsalicylic acid within a variety of different organic solutions: methanol, ethanol, propan-2-ol, acetonitrile, tetrahydrofuran and 1,4-dioxane. With the use of gradient elution chromatography and mass spectrometry detection in negative ionization, MS and MS/MS spectra were recorded simultaneously. In addition, quantitative, as well as qualitative analysis was performed during one assay. The stability of acetylsalicylic acid in such solutions was tested at room temperature, in a 12h period. In the work, in all cases, only one main degradation product, salicylic acid, was found. What is more, the work revealed that the degradation of aspirin in the tested organic solutions yields apparent second-order kinetics. The study also demonstrated that acetonitrile and 1,4-dioxane turned out to be the most stable solvents, and an above 80% of initial concentration of acetylsalicylic acid was found in this case. Furthermore, the most popular analytical solvents, methanol and ethanol, were found to be very unstable media. Herein, below 40% of initial concentration of acetylsalicylic acid was seen after 12h. The obtained results were also compared with the degradation of acetylsalicylic acid in a water solution. In this situation, only about 25% of the analyzed compound was resolved to salicylic acid in the same time frame.

For the first time, the influence of ionising radiation on the physicochemical properties of ertapenem in solid state was studied. During our studies, we evaluated the possibility of applying radiosterilization to obtain sterile ertapenem. Spectroscopic (Fourier Transform Infrared (FT-IR)), thermal (differential scanning calorimetry (DSC), chromatography (High-Performance Liquid Chromatography (HPLC) and HPLC-MS), and X-ray powder diffraction (XRPD) studies shown that irradiation of ertapenem with the 25 kGy, the dose required to achieve sterility, does not change the physicochemical properties of the studied compound. The antimicrobial activity of ertapenem irradiated with the dose of 25 kGy was only reduced for one species. Based on the received results, we can conclude that radiostelization is a promising alternative method of obtaining sterile ertapenem. In our studies, ertapenem was also exposed to e-beam radiation with a dose of 400 kGy. It was determined that two novel degradation products that are structurally differently to degradants formed during hydrolysis and thermolysis.

A procedure for the screening and quantification of 18 glucocorticoids, i.e. hydrocortisone sodium succinate (HSS), prednisolone (PDL), prednisone (PDS), hydrocortisone (HCS), methylprednisolone (MPS), betamethasone (BTM), dexamethasone (DXM), triamcinolone acetonide (TA), prednisolone acetate (PLA), hydrocortisone acetate (HA), fludrocortisone acetate (FA), prednisone acetate (PA), cortisone acetate (CA), dexamethasone acetate (DA), hydrocortisone butyrate (HB), triamcinolone acetonide acetate (TAA), fluocinonide (FN) and halcinonide (HC) from herbal pharmaceuticals and health foods was established and fully validated. The samples were extracted by methanol and separated by HPLC. The retention times and ultraviolet spectra were used for the preliminary screening, and the suspected adulterants were then confirmed by liquid chromatography-quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS/MS) and quantified by HPLC. The developed procedure was successfully applied to 14 herbal samples, and 316.3 µg g-1 of DA and 13.6 µg mL-1 of BTM were found in a tablet sample and a spray sample, respectively. To our best knowledge, this is the first report of the simultaneous screening and quantification of these 18 glucocorticoids from any matrix. [ABSTRACT FROM AUTHOR]

Background: Toddalia asiatica root bark as an effective hemostatic natural medicine or Chinese materia medica was applied in China for long history, its complex drug action mechanisms and unclear substance basis have been constraining the development of this drug. Results: An intelligentized strategy by LC-ESI Q-TOF MS was presented in this study for rapid identification of hemostatic chemical constituents from this natural medicine. Chromatographic separation was performed on a C18 column (150 mm × 2.1 mm, 1.8 μm), the MS data in both negative and positive ion modes were acquired to record the high-accuracy MS and MS/MS data of all precursor ions. To reduce the false positive identifications, structural confirmation was conducted by comparison with the isolated reference standards (t and MS, MS/MS data) or matching with natural product databases. Bioassay-guided fractionation of the extract of T. asiatica root bark was also carried out. Conclusions: As a consequence, 31 natural compounds in T. asiatica root bark got putatively characterized. There were four main coumarins, isopimpinellin (Cp.23), pimpinellin (Cp.24), coumurrayin (Cp.30) and phellopterin (Cp.34) isolated and identified from T. asiatica root bark. The present study provided candidate strategy that helps to effectively identify the primary natural compounds of TCM or other complex natural medicines, and then promote development and application of natural medicines and their medicinal resources. [ABSTRACT FROM AUTHOR]

Ultra high-performance liquid chromatography (UHPLC) coupled with highresolution quadrupole time-of-flight (Q-TOF) mass spectrometry was used for the preliminary photodegradation study of nine new generation psychotropic drugs. Based on the above method, two ionization sample modes - electrospray and atmospheric pressure chemical ionization were used for the registration of photodegradation profiles of the selected drugs. Multivariate chemometric analysis showed that electrospray ionization (ESI) method is more specific than atmospheric pressure chemical ionization (APCI) in high-resolution mass spectrometry (HR-MS) analysis of the analyzed psychotropic drugs. It was noticed that, with the use of ESI method, more potential photodegradation products can be identified and lower limits of its detection can be obtained. [ABSTRACT FROM AUTHOR]

The influence of ionising radiation on the physicochemical properties of meropenem trihydrate in solid state was studied for doses of e-beam radiation: 25 kGy and 400 kGy. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile meropenem. No changes for meropenem irradiated with a dose of 25 kGy, the dose required to attain sterility, was confirmed in the results of spectroscopic (FT-IR), thermal (DSC, TGA) and X-ray powder diffraction (XRPD) studies. The radiation dose of 25 kGy produces no more than about 1500 ppm of radical defects. The chromatographic studies of irradiated meropenem in solutions did not show any chemical degradation. Moreover, the antimicrobial activity of meropenem irradiated with the dose of 25 kGy was unchanged. Based on the received results, we can conclude that radiostelization is a promising, alternative method for obtaining sterile meropenem. In the second part of the research, meropenem was exposed to e-beam radiation at the 400 kGy dose rate. It was confirmed, that reducing of antimicrobial activity could be connected with the degradation of β-lactam ring and changes in the trans-hydroxyethyl group. Apart from chemical changes, changes in the physical stability of irradiated meropenem (400 kGy) was also observed.

[Display omitted] • 113% increase in Bisphenol A removal efficiency and 1100% increase in hydrogen peroxide yield. • Favorable stability in hydrogen peroxide yield and Bisphenol A removal at a wide pH range. • Polydopamine improves hydrogen peroxide yield by inhibiting the four-electron reduction reaction of oxygen. • Degradation pathway of Bisphenol A was proposed. Electrocatalytic processes, are greatly limited by acid conditions during water/wastewater treatment, and lead to higher disposal costs. Herein, based on the principle of strong adhesion of invertebrate mussels, polydopamine with multiple functional groups was immobilized on graphite sheet electrodes for constructing the electrocatalytic system (GS-PDA), which achieved favorable stability in hydrogen peroxide (H 2 O 2) yield and model pollutant Bisphenol A (BPA) removal at pH = 3–9. At natural pH (∼5.8), GS-PDA had a higher BPA removal efficiency with 113 % increase in degradation rate and an 1100 % increase in productivity of H 2 O 2 than control group. O 2 bubbling was the original contributor of oxidant and its two-electron reduction product (H 2 O 2) had a significant contribution for BPA removal in GS-PDA. High pH (pH ≥ 5) increased the selectivity toward the four-electron oxygen reduction process (to H 2 O) in control group, while GS-PDA could inhibit this process, thus promoting the production of H 2 O 2 from two-electron oxygen reduction process. Both hydroxyl radicals and singlet oxygen were effective in removing BPA and the former was the primary pathway. Furthermore, 18 dominant degradations were identified in GS-PDA by high resolution hybrid quadrupole time-of-flight mass spectrometer, and BPA degradation pathway was proposed. This work found a way to decrease the effects of pH on electrocatalytic purification of water and generation of H 2 O 2 , and provided a strategy for treating wastewater at neutral pH. [ABSTRACT FROM AUTHOR]

Forced Degradation of Deflazacort drug substance in ultraviolet light condition resulted into a number of significant degradation products. Two of these degradation products were found to be unknown during the study and marked as DD-I and DD-II. Thus, the objective of this work is to investigate and identify these two novel degradation products of DFZ. The isolation method for these new degradation products were developed using a new reverse-phase high performance liquid chromatography (HPLC). DD-I and DD-II, eluting at 0.53 and 1.57 relative retention times with respect to Deflazacort (DFZ) peak respectively, were isolated from reaction mass using preparative HPLC and their structures were elucidated using high resolution MS, multidimensional NMR and FTIR spectroscopic techniques. To best of our knowledge, these two degradation products are novel impurities which are not discussed in any form of publication yet. [ABSTRACT FROM AUTHOR]