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Vepdegestrant (formerly ARV-471), a novel proteolysis-targeting chimera (PROTAC), targets estrogen receptor alpha (ERα) for degradation, offering a promising option to treat advanced ER-positive breast cancer. We developed and validated a sensitive and rapid liquid chromatography–tandem mass spectrometry method to quantify vepdegestrant in rodent plasma using bavdegalutamide (formerly ARV-110) as an internal standard. Plasma samples were prepared with protein precipitation using acetonitrile and analyzed using reverse-phase C18 columns and a mobile phase of 10 mM ammonium formate in distilled water and acetonitrile. The method demonstrated linearity from 1 to 1000 ng/mL in mouse and rat plasma, meeting all validation criteria, and successfully applied to in vivo and in vitro studies. Pharmacokinetic analysis revealed low-to-moderate clearance (313.3, 1053 mL/h/kg) and oral bioavailability (17.91, 24.12%) of vepdegestrant in mice and rats, respectively. It was unstable in buffer solutions across pH 2–10 and in phosphate-buffered saline (pH 7.4), likely due to adsorption, but remained stable in mouse and rat plasma at varying temperatures. In liver microsomes, vepdegestrant exhibited moderate stability in rats but was stable in mice, dogs, and humans. These findings enhance the understanding of pharmacokinetic properties of vepdegestrant supporting further development of PROTAC drugs. [ABSTRACT FROM AUTHOR]

The chemical compounds found in propolis vary according to plant sources, species, and geographical regions. To date, Indonesian propolis has not yet become standardized in terms of its chemical constituents. Thus, this study aimed to identify the presence of marker compounds and determine whether different classes of Indonesian propolis exist. In this study, yields, total polyphenol content (TPC), total flavonoid content (TFC), and antioxidants were measured. Identification of chemical compounds was carried out with Fourier-transform infrared (FTIR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metaboanalyst 6.0 was employed in conducting principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using the results of the FTIR and LC-MS/MS. The propolis with the highest TFC, TPC, and antioxidant activity was Geniotrigona thoracica from North Sumatra. The results of propolis compound mapping based on region with discriminant analysis revealed that types of propolis from Java have similar characteristics. Then, based on species, the types of propolis from Tetragonula laeviceps and Heterotrigona itama have special characteristics; the samples from these species can be grouped according to similar characteristics. In conclusion, 10 potential marker compounds were identified in Indonesian propolis, enabling regional and species-specific varieties of Indonesian propolis to be classified based on chemical composition mapping. [ABSTRACT FROM AUTHOR]

Morus alba L. is a tradition medical and edible plant. It is rich in many important bioactive components. However, there is a dearth of systematic information about the components. Here, the Mori Cortex, Mori Folium, Mori Fructus, and Mori Ramulus were studied. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC–MS) is used to study primary and secondary metabolites. Eight hundred two metabolites were identified and classified into 10 different categories in total. Correlation analysis, hierarchical clustering analysis, and principal component analysis of metabolites showed that different parts of the sample could be significantly different. In different medicinal parts, alkaloids accounted for 4.0%, 3.6%, 5.1%, and 4.5%; flavonoids accounted for 0.7%, 27.2%, 5.6%, 1.2%; terpenes accounted for 20.1%, 2.1%, 2.6%, 2.5%. Furthermore, the abundance of phenols, phenylpropanoids, and lipids metabolites sequentially accounted for 2.3–4.4%, 0.5–1.8%, and 2.4–5.3%. These results have improved our understanding of metabolites and provided a reference for research on the medicinal and edible value of Morus alba L. In addition, the study reveals the correlation between the components of Traditional Chinese medicine and the basic theory of TCM properties and reinterprets the ancient wisdom in the world's traditional herbs through the perspective of modern science. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Its treatment options have had a limited impact on cancer remission prognosis. Therefore, there is an ongoing need to discover novel anti-cancer agents. Medicinal plants have gained recognition as a source of anti-cancer bioactive compounds. Recently, ethanolic extract of L. virginicum stems ameliorated dinitrobenzene sulfonic acid (DNBS)-induced colitis by modulating the intestinal immune response. However, no scientific study has demonstrated this potential cytotoxic impact on colon cancer cells. The objective of this study was to evaluate the cytotoxic effect of the methanolic extract of L. virginicum (ELv) on a human colorectal adenocarcinoma cell line (Caco-2) and to identify and quantify the phenolic compounds present in ELv extracts by liquid chromatography-mass spectrometry analysis. The cytotoxic activity was assessed using cell viability assays by reduction in the compound 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH). MTT and LDH assays revealed that the ELv decreases cell viability in the Caco-2 cell line in a concentration-dependent manner. Cell death was a result of DNA fragmentation and p53-mediated apoptosis. Eight phenolic acids and five flavonoids were identified and quantified in the stems. In conclusion, our findings demonstrate that the extract of L. virginicum possesses cytotoxic properties on Caco-2 cell line, suggesting that it could be a potential source of new drugs against CRC. [ABSTRACT FROM AUTHOR]

Among the various compounds regarded as emerging contaminants (ECs), pharmaceuticals and personal care products (PPCPs) are of particular concern. Their continuous release into the environment has a negative global impact on human life. This review summarizes the sources, occurrence, persistence, consequences of exposure, and toxicity of PPCPs, and evaluates the various analytical methods used in the identification and quantification of PPCPs in a variety of solid and liquid environmental matrices. The current techniques of choice for the analysis of PPCPs are state-of-the-art liquid chromatography coupled to mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS2). However, the complexity of the environmental matrices and the trace levels of micropollutants necessitate the use of advanced sample treatments before these instrumental analyses. Solid-phase extraction (SPE) with different sorbents is now the predominant method used for the extraction of PPCPs from environmental samples. This review also addresses the ongoing analytical method challenges, including sample clean-up and matrix effects, focusing on the occurrence, sample preparation, and analytical methods presently available for the determination of environmental residues of PPCPs. Continuous development of innovative analytical methods is essential for overcoming existing limitations and ensuring the consistency and diversity of analytical methods used in investigations of environmental multi-class compounds. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) is a widely used analytical technique including medical diagnostics, forensic toxicology, food and water analysis. The gold standard for quantifying compounds involves using stable isotope-labeled internal standards (SIL-IS). However, when these standards are not commercially available, are prohibitively expensive, or are extremely difficult to synthesize, alternative external quantification techniques are employed. We hereby present a novel, convenient and cheap quantification approach—quantification via post column infusion (PCI). As a proof of concept, we demonstrated PCI quantification for the immunosuppressant tacrolimus in whole blood using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The validation results met the criteria according to the guideline on bioanalytical method validation of the European Medicine Agency (EMA), achieving imprecisions and inaccuracies with coefficient of variation and relative bias below 15%. Anonymized and leftover whole blood samples from immunosuppressed patients receiving tacrolimus were used for method comparison (PCI quantification vs. conventional internal standard (IS) quantification). Both methods showed strong agreement with a Pearson correlation coefficient of r = 0.9532. This novel PCI quantification technique (using the target analyte itself) expands the quantification options available in MS, providing reliable results, particularly when internal standards are unavailable or unaffordable. With the current paper, we aim to demonstrate that our innovative PCI technique has great potential to overcome practical issues in quantification and to provide guidance on how to incorporate PCI in existing or new LC-MS methods. Moreover, this study demonstrated a more convenient method for correcting matrix effects in comparison to alternative PCI techniques. [ABSTRACT FROM AUTHOR]

Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3′-hydroxycotinine, and (2′S)-nicotine 1'-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans-3′-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1′S,2′S)-nicotine 1′-oxide in the samples of individuals from various groups. [ABSTRACT FROM AUTHOR]

The aim of individuals consuming health supplements is to attain a robust state through nutritional regulation. However, some unscrupulous manufacturers, motivated by profit, fraudulently incorporate drugs or unauthorized components with therapeutic effects into the product for instant product performance enhancement. The long-term use of these products may inadvertently inflict harm on human health and fail to promote nutritive healthcare. The illegal inclusion of these substances is prevalent in kidney-tonifying and sexuality-enhancing products. Developing effective analytical methods to identify these products and screen for illegal added ingredients can effectively prevent such products from reaching and remaining on the market. A target screening method for the detection and quantification of 90 phosphodiesterase type 5 inhibitors (PDE-5is) in 5 kinds of health products was developed and validated. The type of dietary supplements varied from tablets, capsules, and protein powder to wine and beverages. Sample preparation was completed with a one-step liquid phase extraction. The screening process of 90 PDE-5is was done efficiently within 25 min by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using the dynamic multiple reaction monitoring (dMRM) technique. The LODs of 90 PDE-5is were detected at levels ranging from 25 to 85 ng/g or ng/mL. This novel targeting methodology was effective and can be applied to routine market supervision. Among 286 batches of samples, 8 batches were found to be positive. Three kinds of PDE-5is were first detected in healthy products. The screening method demonstrated herein will be a promising and powerful tool for rapid screening of PDE-5is. [ABSTRACT FROM AUTHOR]

In the past, polyacrylamide hydrogel was a popular choice for breast augmentation filler, and many women underwent mammoplasty with this gel. However, due to frequent complications, the use of polyacrylamide hydrogel in mammoplasty has been banned. Despite this ban, patients experiencing complications still seek medical treatment. The aim of this study was to investigate the fate of the polymer over a defined implantation period. Biopsies of breast implants were obtained from patients with 23 and 27 years of post-mammoplasty. These biopsies were meticulously purified from biological impurities and subjected to analysis using IR spectrometry, liquid chromatography—mass spectrometry, gas chromatography, and differential scanning calorimetry. The findings revealed the presence of polyacrylamide hydrogel residues, along with degradation products, within the infected material. Notably, the low-molecular-weight degradation products revealed via gas chromatography are aggressive and toxic substances capable of inducing chronic inflammation. This study sheds light on the long-term consequences of polyacrylamide hydrogel implantation, highlighting the persistence of harmful degradation products and their role in exacerbating patient complications. [ABSTRACT FROM AUTHOR]

The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human health. The aim of this study was to develop a sensitive and selective method using fully automatic solid-phase extraction coupled with ultra-performance liquid chromatography–tandem mass spectrometry for the determination of twelve TCs in water. Four isotope-labeled internal standards for TCs were used to correct matrix effects. Several parameters affecting extraction efficiency were systematically optimized, and the optimum experimental conditions found were 1.0 L water sample with 0.5 g/L Na2EDTA (pH 3.0) extracted and enriched by CNW HLB cartridge and eluted by 4 mL of acetone:methanol (v/v, 1:1). The enrichment factors were up to 798−1059 but only requiring about 60 min per six samples. Under the optimized conditions, the linearity of the method ranged from 0.2 to 100 μg/L for 12 TCs, the detection limits were as low as 0.01−0.15 ng/L, and the recoveries were in the range of 70%–118%, with relative standard deviations less than 15%. The developed method can be successfully utilized for the determination of 12 TCs in pure water, tap water, river water, and mariculture seawater. In summary, three and six TCs were detected in river water and mariculture seawater, respectively, with total concentrations of 0.074–0.520 ng/L (mean 0.248 ng/L) and 0.792–58.369 ng/L (12.629 ng/L), respectively. Tetracycline (TC) and oxytetracycline (OTC) were the dominant TCs in river water, while doxytetracycline (DXC) and OTC were dominant in mariculture seawater. [ABSTRACT FROM AUTHOR]

A promising method was established for the determination of nine halobenzoquinones (HBQs) in potable water by membrane solid-phase extraction (MSPE) pretreatment and the liquid chromatography–mass spectrometry (LC-MS) method. A 500 mL water sample was taken for enrichment by the SDB-RPS membrane, which was previously activated by methanol and ultrapure water. The sample was eluted with methanol and re-dissolved with the initial mobile phase after nitrogen blowing. Then, it was detected in negative ion mode using the working curve, and HBQs were quantified by the external standard method. The linearity was satisfactory in the concentration range of 4-1000 ng/L, with correlation coefficients of 0.9963~0.9994. The recoveries were 73.5~126.6% at three spiked levels, with relative standard deviations (RSDs) of 6.8~15.5%. The limits of detection (LOD, S/N = 3) values were 0.1~0.7 ng/L. The results demonstrate that the MSPE-LC-MS method is reliable, rapid, and sensitive for the simultaneous analysis of nine HBPs in potable water. [ABSTRACT FROM AUTHOR]

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography–mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material–solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1β in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods. [ABSTRACT FROM AUTHOR]

Due to the intricate complexity of the original microbiota, residual heat-resistant enzymes, and chemical components, identifying the essential factors that affect dairy quality using traditional methods is challenging. In this study, raw milk, pasteurized milk, and ultra-heat-treated (UHT) milk samples were collectively analyzed using metagenomic next-generation sequencing (mNGS), high-throughput liquid chromatography-mass spectrometry (LC-MS), and gas chromatography–mass spectrometry (GC-MS). The results revealed that raw milk and its corresponding heated dairy products exhibited different trends in terms of microbiota shifts and metabolite changes during storage. Via the analysis of differences in microbiota and correlation analysis of the microorganisms present in differential metabolites in refrigerated pasteurized milk, the top three differential microorganisms with increased abundance, Microbacterium (p < 0.01), unclassified Actinomycetia class (p < 0.05), and Micrococcus (p < 0.01), were detected; these were highly correlated with certain metabolites in pasteurized milk (r > 0.8). This indicated that these genera were the main proliferating microorganisms and were the primary genera involved in the metabolism of pasteurized milk during refrigeration-based storage. Microorganisms with decreased abundance were classified into two categories based on correlation analysis with certain metabolites. It was speculated that the heat-resistant enzyme system of a group of microorganisms with high correlation (r > 0.8), such as Pseudomonas and Acinetobacter, was the main factor causing milk spoilage and that the group with lower correlation (r < 0.3) had a lower impact on the storage process of pasteurized dairy products. By comparing the metabolic pathway results based on metagenomic and metabolite annotation, it was proposed that protein degradation may be associated with microbial growth, whereas lipid degradation may be linked to raw milk's initial heat-resistant enzymes. By leveraging the synergy of metagenomics and metabolomics, the interacting factors determining the quality evolution of dairy products were systematically investigated, providing a novel perspective for controlling dairy processing and storage effectively. [ABSTRACT FROM AUTHOR]

Itampolin A, a natural brominated tyrosine alkaloid isolated from the sponge Iotrochota purpurea, has been shown to have good inhibitory effects in lung cancer cells as a p38α inhibitor. A simple, sensitive, and reliable ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method has been established, validated, and applied to the study of the pharmacokinetics and tissue distribution of itampolin A following intragastric and intravenous administration. Itampolin A and theophylline (internal standard, IS) were extracted by the simple protein precipitation technique using methanol as the precipitating solvent. Chromatographic separation was achieved by using the optimized mobile phase of a 0.1% formic acid aqueous solution and acetonitrile in the gradient elution mode. Itampolin A and IS were detected and quantified using positive electrospray ionization in the multiple reaction monitoring mode with transitions of m/z 863.9 → 569.1 for itampolin A and m/z 181.1 → 124.1 for IS, respectively. The assay exhibited a linear dynamic range of 1–1600 ng/mL for itampolin A in biological samples and the low limit of quantification was 1 ng/mL. Non-compartmental pharmacokinetic parameters indicated that itampolin A was well-absorbed into the systemic circulation and rapidly eliminated after administration. The apparent distribution volume of itampolin A was much higher after intragastric administration than that after intravenous administration. A tissue distribution study showed that itampolin A could be detected in different tissues and maintained a high concentration in the lung, which provided a material basis for its effective application in lung cancer. The pharmacokinetic process and tissue distribution characteristics of imtapolin A were expounded in this study, which can provide beneficial information for the further research and clinical application of itampolin A. [ABSTRACT FROM AUTHOR]

Callus cultures of the Iranian medicinal plant Salvia atropatana were initiated from three-week-old seedlings on Murashige and Skoog (MS) medium supplemented with α-naphthaleneacetic acid (NAA) and various cytokinins. Although all tested hormonal variants of the medium and explant enabled callus induction, the most promising growth was noted for N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU)-induced calli. Three lines obtained on this medium (cotyledon line-CL, hypocotyl line—HL, and root line—RL) were preselected for further studies. Phenolic compounds in the callus tissues were identified using UPLC–MS (ultra-performance liquid chromatography–mass spectrometry) and quantified with HPLC (high-performance liquid chromatography). All lines exhibited intensive growth and contained twelve phenolic acid derivatives, with rosmarinic acid predominating. The cotyledon-derived callus line displayed the highest growth index values and polyphenol content; this was exposed to different light-emitting diodes (LED) for improving biomass accumulation and secondary metabolite yield. Under LED treatments, all callus lines exhibited enhanced RA and total phenolic content compared to fluorescent light, with the highest levels observed for white (48.5–50.2 mg/g dry weight) and blue (51.4–53.9 mg/g dry weight) LEDs. The selected callus demonstrated strong antioxidant potential in vitro based on the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) tests. Our findings confirm that the S. atropatana callus system is suitable for enhanced rosmarinic acid production; the selected optimized culture provide high-quality plant-derived products. [ABSTRACT FROM AUTHOR]

The investigation of collagen hydrolysates (CHs) is essential due to their widespread use in health, cosmetic, and therapeutic industries, attributing to the presence of bioactive dipeptides (DPs) and tripeptides (TPs). This study developed a novel targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) method with propyl chloroformate (PCF) derivatization to measure three bioactive peptides—Hydroxyprolyl-glycine (Hyp-Gly), Glycyl-prolyl-hydroxyproline (Gly-Pro-Hyp), and Prolyl-hydroxyproline (Pro-Hyp)—in CHs, with strong correlation coefficients (0.992, 1.000, and 0.995, respectively) and low limits of detection (LODs) of 1.40, 0.14, and 1.16 µM, respectively. Untargeted data-dependent acquisition (DDA) analyses measured peptide size distribution, while amino acid analysis assessed nutritional content. The analysis of ten commercial CHs revealed similar amino acid profiles but varied peptide lengths, indicating diverse hydrolysis conditions. Products with higher proportions of smaller peptides showed elevated levels of the targeted bioactive peptides, suggesting that a smaller peptide size may increase bioactivity. These findings can inform the optimization of CH supplements, providing consumers with detailed peptide content for more informed choices. Data are available via ProteomeXchange with the identifier PXD051699. [ABSTRACT FROM AUTHOR]

Acetic acid bacteria (AAB) and other members of the complex microbiotas, whose activity is essential for vinegar production, display biodiversity and richness that is difficult to study in depth due to their highly selective culture conditions. In recent years, liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) has emerged as a powerful tool for rapidly identifying thousands of proteins present in microbial communities, offering broader precision and coverage. In this work, a novel method based on LC–MS/MS was established and developed from previous studies. This methodology was tested in three studies, enabling the characterization of three submerged acetification profiles using innovative raw materials (synthetic alcohol medium, fine wine, and craft beer) while working in a semicontinuous mode. The biodiversity of existing microorganisms was clarified, and both the predominant taxa (Komagataeibacter, Acetobacter, Gluconacetobacter, and Gluconobacter) and others never detected in these media (Asaia and Bombella, among others) were identified. The key functions and adaptive metabolic strategies were determined using comparative studies, mainly those related to cellular material biosynthesis, energy-associated pathways, and cellular detoxification processes. This study provides the groundwork for a highly reliable and reproducible method for the characterization of microbial profiles in the vinegar industry. [ABSTRACT FROM AUTHOR]

Over the years, there has been notable progress in understanding the pathogenesis and treatment modalities of diabetes and its complications, including the application of metabolomics in the study of diabetes, capturing attention from researchers worldwide. Advanced mass spectrometry, including gas chromatography–tandem mass spectrometry (GC-MS/MS), liquid chromatography–tandem mass spectrometry (LC-MS/MS), and ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), etc., has significantly broadened the spectrum of detectable metabolites, even at lower concentrations. Advanced mass spectrometry has emerged as a powerful tool in diabetes research, particularly in the context of metabolomics. By leveraging the precision and sensitivity of advanced mass spectrometry techniques, researchers have unlocked a wealth of information within the metabolome. This technology has enabled the identification and quantification of potential biomarkers associated with diabetes and its complications, providing new ideas and methods for clinical diagnostics and metabolic studies. Moreover, it offers a less invasive, or even non-invasive, means of tracking disease progression, evaluating treatment efficacy, and understanding the underlying metabolic alterations in diabetes. This paper summarizes advanced mass spectrometry for the application of metabolomics in diabetes mellitus, gestational diabetes mellitus, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic encephalopathy, diabetic cardiomyopathy, and diabetic foot ulcers and organizes some of the potential biomarkers of the different complications with the aim of providing ideas and methods for subsequent in-depth metabolic research and searching for new ways of treating the disease. [ABSTRACT FROM AUTHOR]

Aspergillus cristatus is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography–mass spectrometry (LC–MS) combined with multivariate analysis was performed to analyze the distribution and composition of A. cristatus under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC–MS metabolomics analysis revealed significant differences between three A. cristatus mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of A. cristatus mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that A. cristatus adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition. [ABSTRACT FROM AUTHOR]

Photosensitizers cause oxidative damages in various biological systems under light. In this study, the method for analyzing photosensitizing activity of various dietary and medicinal sources was developed using 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (thiazolyl blue formazan; MTT-F) as a probe. Significant and quantitative decolorization of MTT-F was observed in the presence of photosensitizers used in this study under light but not under dark conditions. The decolorization of MTT-F occurred irradiation time-, light intensity-, and photosensitizer concentration-dependently. The decolorized MTT-F was reversibly reduced by living cells; the LC-MS/MS results indicated the formation of oxidized products with −1 m/z of base peak from MTT-F, suggesting that MTT-F decolorized by photosensitizers was its corresponding tetrazolium. The present results indicate that MTT-F is a reliable probe for the quantitative analysis of photosensitizing activities, and the MTT-F-based method can be an useful tool for screening and evaluating photosensitizing properties of various compounds used in many industrial purposes. [ABSTRACT FROM AUTHOR]

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening. [ABSTRACT FROM AUTHOR]

Utilizing online gradient pressure liquid extraction (OGPLE) coupled with a high-performance liquid chromatography antioxidant analysis system, we examined the antioxidative active components present in both the aerial parts and roots of dandelion. By optimizing the chromatographic conditions, we identified the ferric reducing–antioxidant power system as the most suitable for online antioxidant reactions in dandelion. Compared to offline ultrasonic extraction, the OGPLE method demonstrated superior efficiency in extracting chemical components with varying polarities from the samples. Liquid chromatography–mass spectrometry revealed twelve compounds within the dandelion samples, with nine demonstrating considerable antioxidant efficacy. Of these, the aerial parts and roots of dandelion contained nine and four antioxidant constituents, respectively. Additionally, molecular docking studies were carried out to investigate the interaction between these nine antioxidants and four proteins associated with oxidative stress (glutathione peroxidase, inducible nitric oxide synthase, superoxide dismutase, and xanthine oxidase). The nine antioxidant compounds displayed notable binding affinities below −5.0 kcal/mol with the selected proteins, suggesting potential receptor–ligand interactions. These findings contribute to enhancing our understanding of dandelion and provide a comprehensive methodology for screening the natural antioxidant components from herbs. [ABSTRACT FROM AUTHOR]

In the past few decades, considerable scientific strides have been made in the subject of drug analysis in human biological samples. However, the risk caused by incorrect drug plasma levels in patients still remains an important concern. This review paper attempts to investigate the advances made over the last ten years in common sample preparation techniques (SPT) for biological samples based on solid sorbents, including solid-phase extraction (SPE) and solid-phase micro-extraction (SPME), and in particular in the field of molecularly imprinted polymers (MIPs), including non-stimuli-responsive and stimuli-responsive adsorbents. This class of materials is known as 'smart adsorbents', exhibiting tailored responses to various stimuli such as magnetic fields, pH, temperature, and light. Details are provided on how these advanced SPT are changing the landscape of modern drug analysis in their coupling with liquid chromatography-mass spectrometry (LC-MS) analytical techniques, a general term that includes high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC), as well as any variation of MS, such as tandem (MS/MS), multiple-stage (MSn), and high-resolution (HRMS) mass spectrometry. Some notes are also provided on coupling with less-performing techniques, such as high-performance liquid chromatography with ultraviolet (HPLC-UV) and diode array detection (HPLC-DAD) detection. Finally, we provide a general review of the difficulties and benefits of the proposed approaches and the future prospects of this research area. [ABSTRACT FROM AUTHOR]

Sulfite, a widely used food additive, is subject to regulated labeling. The extraction of sulfite as the stable hydroxymethylsulfonate (HMS) form and its quantitative analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized for their good sensitivity, selectivity, and versatility across various food materials. This study aimed to develop a cost-effective and simpler method for sulfite quantitation, while maintaining the superior sensitivity and selectivity of mass spectrometry (MS). To achieve this, we introduced paper spray ionization (PSI), an ambient desorption ionization technique that could achieve the direct measurement of analytes without employing separation. We also employed a novel internal standard (IS) structurally similar to the analyte, replacing the more expensive isotopically labeled IS. Although the PSI-MS/MS method developed in this study exhibited slightly lower analytical performance compared to the conventional LC-MS/MS, it remained effective for sulfite analysis in dried fruits. [ABSTRACT FROM AUTHOR]

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1β in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines. [ABSTRACT FROM AUTHOR]

This study presents a method for analyzing dimethomorph residues in lychee using QuEChERS extraction and HPLC-MS/MS. The validation parameters for this method, which include accuracy, precision, linearity, and recovery, indicate that it meets standard validation requirements. Following first-order kinetics, the dissipation dynamic of dimethomorph in lychee was determined to range from 6.4 to 9.2 days. Analysis of terminal residues revealed that residues in whole lychee were substantially greater than those in the pulp, indicating that dimethomorph residues are predominantly concentrated in the peel. When applied twice and thrice at two dosage levels with pre-harvest intervals (PHIs) of 5, 7, and 10 days, the terminal residues in whole lychee ranged from 0.092 to 1.99 mg/kg. The terminal residues of the pulp ranged from 0.01 to 0.18 mg/kg, with the residue ratio of whole lychee to pulp consistently exceeding one. The risk quotient (RQ) for dimethomorph, even at the recommended dosage, was less than one, indicating that the potential for damage was negligible. This study contributes to the establishment of maximum residue limits (MRLs) in China by providing essential information on the safe application of dimethomorph in lychee orchards. [ABSTRACT FROM AUTHOR]

Currently, the planting of 'Qi-Nan' is continuously increasing, yet a substantial amount of 'Qi-Nan' leaves have not been properly exploited. To improve the 'Qi-Nan' tree 's utilization value, 'Qi-Nan' leaves were used as a raw material. An ultrasound-assisted method was performed to obtain the flavonoids from the 'Qi-Nan' leaves, followed by optimization of the extraction factors using a one-way and response surface methodology to enhance the extraction of flavonoids. Subsequently, the composition of the flavonoids, as well as their bioactive abilities, were analyzed by ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS) and in vitro activity testing methods. The findings demonstrated that a 1:50 material-to-liquid ratio, 60% ethanol concentration, and ultrasound-assisted extraction time of 30 min were the ideal procedures for extracting flavonoids (flavonoid content: 6.68%). Meanwhile, the 'Qi-Nan' leaves possessed the antioxidant and medicinal potential to prevent diabetes and Alzheimer 's disease, as evidenced by the semi-inhibitory concentrations (IC50 values) of flavonoid extracts for scavenging DPPH• free radicals, scavenging ABTS•+ free radicals, inhibiting acetylcholinesterase, and inhibiting α-glucosidase, which were 12.64 μg/mL, 66.58 μg/mL, 102.31 μg/mL, and 38.76 μg/mL, respectively, which indicated that the 'Qi-Nan' leaves possessed the properties of antioxidant and medicinal potential for the prevention of Alzheimer 's disease and diabetes. [ABSTRACT FROM AUTHOR]

Antibiotics in animal production are widely used around the world for therapeutic and preventive purposes, and in some countries, they still serve as antibiotic growth stimulants. Regardless of the purpose of using antibiotics in livestock, they may be present in animal tissues and organs as well as in body fluids and excretions (feces and urine). Farm animal excrement in unprocessed form (natural fertilizers) or processed form (organic fertilizers) is applied to agricultural fields because it improves soil fertility. Antibiotics present in fertilizers may therefore contaminate the soil, surface, groundwater, and plants, which may pose a threat to the environment, animals, and humans. Therefore, it is important to develop analytical methods that will allow for the control of the presence of antibacterial substances in natural and organic fertilizers. Therefore, in this study, an LC-MS/MS method was developed and validated for the determination of 21 antibacterial substances in natural and organic liquid fertilizers. The developed method was used to analyze 62 samples of natural and organic liquid fertilizers, showing that over 24% of the tested samples were contaminated with antibiotics, mainly from the group of tetracyclines and fluoroquinolones. Studies of post-fermentation sludge from biogas plants have shown that the processes of anaerobic methane fermentation, pH, and temperature changes taking place in bioreactors do not lead to the complete degradation of antibiotics present in the material used for biogas production. For this reason, monitoring studies of natural and organic fertilizers should be undertaken to limit the introduction of antibiotics into the natural environment. [ABSTRACT FROM AUTHOR]

Vitamin D (Vit D) is a fat-soluble molecule acting like a hormone, and it is involved in several biological mechanisms such as gene expression, calcium homeostasis, bone metabolism, immune modulation, viral protection, and neuromuscular functions. Vit D deficiency can lead to chronic hypocalcemia, hyperparathyroidism, and many other pathological conditions; in this context, low and very low levels of 25-hydroxy-vitamin D (25-OH-D) were found to be associated with an increased risk of COVID-19 infection and the likelihood of many severe diseases. For all these reasons, it is important to quantify and monitor 25-OH-D levels to ensure that the serum/blood concentrations are not clinically suboptimal. Serum concentration of 25-OH-D is currently the main indicator of Vit D status, and it is currently performed by different assays, but the most common quantitation techniques involve immunometric methods or chromatography. Nevertheless, other quantitation techniques and instruments are now emerging, such as AFIAS-1® and AFIAS-10® (Boditech and Menarini) based on the immunofluorescence analyzer, that guarantee an automated system with cartridges able to give quick and reliable results as a point-of-care test (POCT). This work aims to compare AFIAS-1® and AFIAS-10® (Boditech and Menarini) Vit D quantitation with Ultra High-Performance Liquid Chromatography coupled with tandem mass spectrometry that currently represents the gold standard technique for Vit D quantitation. The analyses were performed in parallel on 56 samples and in different conditions (from fresh and frozen plasma) to assess the reliability of the results. Any statistically significant differences in methods, the fixed error, and the error proportional to concentration were reported. Results obtained in all conditions showed a good correlation between both AFIAS® instruments and LC-MS/MS, and we can affirm that AFIAS-1® and AFIAS-10® are reliable instruments for measuring 25-OH-D with accuracy and in a fast manner. [ABSTRACT FROM AUTHOR]

The rhizome of Polygonatum cyrtonema Hua has been used as a traditional Chinese medicine for over 2000 years. The fresh Chinese herb possesses micro toxicity and is thus traditionally alternately steamed and basked nine times to alleviate the toxicity and enhance the pharmaceutical efficacy. Different processing cycles usually result in variable therapeutic effects in the processed Polygonatum cyrtonema Hua (P-PCH). However, it can be hard to tell these various P-PCHs apart at present. To identify the P-PCHs that had undergone repeated steaming one to nine times, the chemical constituents were profiled based on Ultra-Performance Liquid Chromatography with Quadruple-Time-of-Flight Mass Spectrometry, and the Principal Component Analysis and Cluster Analysis methods were adopted to discriminate different cycles of P-PCH. A total of 44 characteristic markers were identified, which allowed the P-PCHs to be discriminated exactly. [ABSTRACT FROM AUTHOR]

Heterogeneous photocatalysis–self-Fenton technology is a sustainable strategy for treating organic pollutants in actual water bodies with high-fluent degradation and high mineralization capacity, overcoming the limitations of the safety risks caused by adding external iron sources and hazardous chemicals in the homogeneous Fenton reaction and injecting high-intensity energy fields in photo-Fenton reaction. Herein, a photo-self-Fenton system based on resorcinol–formaldehyde (RF) resin and red mud (RM) was established to generate hydrogen peroxide (H2O2) in situ and transform into hydroxy radical (•OH) for efficient degradation of tetracycline (TC) under visible light irradiation. The capturing experiments and electron spin resonance (ESR) confirmed that the hinge for the enhanced performance of this system is the superior H2O2 yield (499 μM) through the oxygen reduction process (ORR) of the two-step single-electron over the resin and the high concentration of •OH due to activation effect of RM. In addition, the Fe2+/Fe3+ cycles are accelerated by photoelectrons to effectively initiate the photo-self-Fenton reaction. Finally, the possible degradation pathways were proposed via liquid chromatography-mass spectrometry (LC-MS). This study provides a new idea for environmental recovery in a waste-based heterogeneous photocatalytic self-Fenton system. [ABSTRACT FROM AUTHOR]

A multi-residue UHPLC–MS/MS analytical method, previously developed for monitoring 52 pharmaceuticals in drinking water, was used to analyse these pharmaceuticals in wastewater originating from healthcare facilities in the Czech Republic. Furthermore, the methodology was expanded to include the evaluation of the effectiveness of drug removal in Czech wastewater treatment plants (WWTPs). Of the 18 wastewater samples analysed by the validated UHPLC-MS/MS, each sample contained at least one quantifiable analyte. This study reveals the prevalence of several different drugs; mean concentrations of 702 μg L−1 of iomeprol, 48.8 μg L−1 of iopromide, 29.9 μg L−1 of gabapentin, 42.0 μg L−1 of caffeine and 82.5 μg L−1 of paracetamol were present. An analysis of 20 samples from ten WWTPs revealed different removal efficiencies for different analytes. Paracetamol was present in the inflow samples of all ten WWTPs and its removal efficiency was 100%. Analytes such as caffeine, ketoprofen, naproxen or atenolol showed high removal efficiencies exceeding 80%. On the other hand, pharmaceuticals like furosemide, metoprolol, iomeprol, zolpidem and tramadol showed lower removal efficiencies. Four pharmaceuticals exhibited higher concentrations in WWTP effluents than in the influents, resulting in negative removal efficiencies: warfarin at −9.5%, indomethacin at −53%, trimethoprim at −54% and metronidazole at −110%. These comprehensive findings contribute valuable insights to the pharmaceutical landscape of wastewater from healthcare facilities and the varied removal efficiencies of Czech WWTPs, which together with the already published literature, gives a more complete picture of the burden on the aquatic environment. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids (SCFA) and lactate in ruminal fluid are products resulting from the microbial fermentation of substrates and can be used to reflect the composition and activity of the ruminal microbiome. Determination of SCFA and D-/L-lactate in ruminal fluid currently requires two separate protocols, which is time-consuming and costly. In this study, we have optimised and validated a simple and unified 3-nitrophenylhydrazine (3-NPH) derivatisation protocol and a 20 min chiral-LC-MS method for the simultaneous quantification of all SCFA and D- and L-lactate in ruminal fluid. This method, which requires no sample pretreatment or purification shows adequate sensitivity (limit of detection (LOD): 0.01 µg/mL), satisfactory accuracy (recovery: 88–103%), and excellent reproducibility (relative standard deviation (RSD) for repeated analyses < 3% for most analytes). The application of this method to a cohort of 24 animals allowed us to reveal a large inter-cow variation in ruminal SCFA and lactate level, the concentration range for each species, the widespread correlation between different SCFA, and the strong correlation between D- and L-lactate. [ABSTRACT FROM AUTHOR]

Terminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography–mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study. [ABSTRACT FROM AUTHOR]

Supplementing fish oil is one of the strategies to reduce the risk of cardiovascular disease, the leading cause of death around the world. Contradictorily, fish oil may also contain trimethylamine-N-oxide, a recently emerged risk factor for cardiovascular disease, as well as one of its precursors, trimethylamine. A method suitable for routine quantification of trimethylamine-N-oxide and trimethylamine in fish oil with a quick and easy liquid extraction without derivatization has been developed. Liquid chromatography with tandem mass spectrometry detection was employed along with a zwitterionic hydrophilic interaction liquid chromatography column and a gradient elution with eluents containing 50 mmol/L of ammonium formate. An internal standard (triethylamine) was used for quantification by mass spectrometry with an external calibration. The assay proved high linearity in the ranges of 10 to 100 ng/mL and 100 to 1000 ng/mL for trimethylamine-N-oxide and trimethylamine, respectively. The lowest limit of quantification was determined to be 100 µg/kg for trimethylamine and 10 µg/kg for trimethylamine-N-oxide, with the limit of detection at 5 µg/kg and 0.25 µg/kg, respectively. Accuracy ranged from 106–119%. Precision was below 7% the relative standard deviation for both analytes. The method was successfully applied for the determination of trimethylamine-N-oxide and trimethylamine contents in nine commercially available liquid fish oils and three commercially available fish oil capsules, showing that trimethylamine and trimethylamine-N-oxide are not present in highly refined fish oils. [ABSTRACT FROM AUTHOR]

There is little data on directly measured carboxymethyl lysine (CML) content in Indonesian foods. This study aimed to generate a database of CML values in foods commonly consumed in West Java and West Sumatra. The results were to be used to update our previous estimated CML values. CML values in food samples were measured using high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Food protein content was analyzed by Kjeldahl's method or inferred from the nutrition facts' label. A total of 210 food samples were examined, with the food groups of meat and poultry (1.06 mg CML/100 g edible food), and starchy foods (0.21 mg/100 g edible food) having the highest and lowest mean CML levels, respectively. We found that the foods with the top three highest CML content were fried starch dough (cimol), fried fish crackers, and chicken gulai. The mean of the estimated values (0.80 mg CML/100 g edible food) was higher than the directly measured values (0.66 mg CML/100 g edible food), [p < 0.035]. Conclusion: This database provides information on CML values in Indonesian foods, and can be further used to make a guide policy for the selection of foods to reduce non-communicable diseases. Further measurements are needed on Indonesian dishes to complete the database. [ABSTRACT FROM AUTHOR]

Carotenoids are hydrophobic pigments produced exclusively by plants, fungi, and specific microbes. Microalgae are well suited for the production of valuable carotenoids due to their rapid growth, efficient isoprenoid production pathway, and ability to store these compounds within their cells. The possible markets for bio-products range from feed additives in aquaculture and agriculture to pharmaceutical uses. The production of carotenoids in microalgae is affected by several environmental conditions, which can be utilized to enhance productivity. The current study focused on optimizing the extraction parameters (time, temperature, and extraction number) to maximize the yield of carotenoids. Additionally, the impact of various nitrogen sources (ammonia, nitrate, nitrite, and urea) on the production of lutein and loroxanthin in Scenedesmus obliquus was examined. To isolate the carotenoids, 0.20 g of biomass was added to 0.20 g of CaCO3 and 10.0 mL of ethanol solution containing 0.01% (w/v) pyrogallol. Subsequently, the extraction was performed using an ultrasonic bath for a duration of 10 min at a temperature of 30 °C. This was followed by a four-hour saponification process using a 10% methanolic KOH solution. The concentration of lutein and loroxanthin was measured using HPLC–DAD at 446 nm, with a flow rate of 1.0 mL/min using a Waters YMC C30 Carotenoid column (4.6 × 250 mm, 5 μm). The confirmation of carotenoids after their isolation using preparative chromatography was achieved using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with an atmospheric pressure chemical ionization (APCI) probe and UV–vis spectroscopy. In summary, S. obliquus shows significant promise for the large-scale extraction of lutein and loroxanthin. The findings of this study provide strong support for the application of this technology to other species. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the effects of hydrothermal treatments under mild acid and alkaline conditions on polyphenol release and recovery from wheat bran (WB). After an initial screening of various food-grade substances, strong evidence was raised regarding the potency of citric acid and sodium carbonate to provide WB extracts exceptionally enriched in polyphenols. Thus, these two catalysts were tested under various time and temperature combinations, and the processes were described by linear models based on severity factor. The most effective treatments were those performed with 10% of either citric acid or sodium carbonate, at a constant temperature of 90 °C for 24 h, providing yields in total polyphenols of 23.76 and 23.60 mg g−1 dry mass of ferulic acid equivalents, respectively. Liquid chromatography–mass spectrometry analyses revealed that, while the sodium carbonate treatment afforded extracts enriched in ferulic acid, treatments with citric acid gave extracts enriched in a ferulate pentose ester. The extracts produced from those treatments also exhibited diversified antioxidant characteristics, a fact ascribed to the different polyphenolic composition. To the best of the authors' knowledge, this is the first report demonstrating the effective release of ferulic acid and a ferulate pentose ester from WB, using benign acid and alkali catalysts, such as citric acid and sodium carbonate. [ABSTRACT FROM AUTHOR]

In this study, the performance of a zero-gap flow-through reactor with three-dimensional (3D) porous Ti/RuO2-TiO2@Pt anodes was systematically investigated for the electrocatalytic oxidation of phenolic wastewater, considering phenol and 4-nitrophenol (4-NP) as the target pollutants. The optimum parameters for the electrochemical oxidation of phenol and 4-NP were examined. For phenol degradation, at an initial concentration of 50 mg/L, initial pH of 7, NaCl concentration of 10.0 g/L, current density of 10 mA/cm2, and retention time of 30 min, the degradation efficiency achieved was 95.05%, with an energy consumption of 15.39 kWh/kg; meanwhile, for 4-NP, the degradation efficiency was 98.42% and energy consumption was 19.21 kWh/kg (at an initial concentration of 40 mg/L, initial pH of 3, NaCl concentration of 10.0 g/L, current density of 10 mA/cm2, and retention time of 30 min). The electrocatalytic oxidation of phenol and 4-NP conformed to the pseudo-first-order kinetics model, and the k values were 0.2562 min−1 and 0.1736 min−1, respectively, which are 1.7 and 3.6-times higher than those of a conventional electrolyzer. Liquid chromatography–mass spectrometry (LC–MS) was used to verify the intermediates formed during the degradation of phenol or 4-NP and a possible degradation pathway was provided. The extremely narrow electrode distance and the flow-through configuration of the zero-gap flow-through reactor were thought to be essential for its lower energy consumption and higher mass transfer efficiency. The zero-gap flow-through reactor with a novel 3D porous Ti/RuO2-TiO2@Pt electrode is a superior alternative for the treatment of industrial wastewater. [ABSTRACT FROM AUTHOR]

Bopyeo-tang (BPT) is composed of six medicinal herbs (Morus alba L., Rehmannia glutinosa (Gaertn.) DC., Panax ginseng C.A.Mey., Aster tataricus L.f., Astragalus propinquus Schischkin, and Schisandra chinensis (Turcz.) Baill.) and has been used for the treatment of lung diseases. This study focused on establishing an analytical method that can simultaneously quantify nine target compounds (i.e., hydroxymethylfurfural, mulberroside A, chlorogenic acid, calycosin-7-O-glucoside, 3,5-dicaffeoylquinic acid, quercetin, kaempferol, schizandrin, and gomisin A) from a BPT sample using high-performance liquid chromatography with a photodiode array detector (HPLC–PDA) and ultra-performance liquid chromatography with tandem mass spectrometry (UPLC–MS/MS). The separation of compounds in both analyses was performed on a C18 reversed-phase column using the gradient elution of water–acetonitrile as the mobile phase. In particular, the multiple reaction monitoring mode was applied for quick and accurate detection in UPLC–MS/MS analysis. As a result of analyzing the two methods, HPLC–PDA and UPLC–MS/MS, the coefficient of determination of the regression equation for each compound was ≥0.9952, and recovery was 85.99−106.40% (relative standard deviation (RSD) < 9.58%). Precision testing of the nine compounds was verified (RSD < 10.0%). The application of these analytical assays under optimized conditions for quantitative analysis of the BPT sample gave 0.01–4.70 mg/g. Therefore, these two assays could be used successfully to gather basic data for clinical research and the quality control of BPT. [ABSTRACT FROM AUTHOR]

While numerous Fabaceae seeds are a good nutritional source of high-quality protein, the use of some species is hampered by toxic effects caused by exposure to metabolites that accumulate in the seeds. One such species is the faba or broad bean (Vicia faba L.), which accumulates vicine and convicine. These two glycoalkaloids cause favism, the breakdown of red blood cells in persons with a glucose-6-phosphate dehydrogenase deficiency. Because this is the most common enzyme deficiency worldwide, faba bean breeding efforts have focused on developing cultivars with low levels of these alkaloids. Consequently, quantification methods have been developed; however, they quantify vicine and convicine only and not the derivatives of these compounds that potentially generate the same bio-active molecules. Based on the recognition of previously unknown (con)vicine-containing compounds, we screened the fragmentation spectra of LC-MS/MS data from five faba bean cultivars using the characteristic fragments generated by (con)vicine. This resulted in the recognition of more than a hundred derivatives, of which 89 were tentatively identified. (Con)vicine was mainly derivatized through the addition of sugars, hydroxycinnamic acids, and dicarboxylic acids, with a group of compounds composed of two (con)vicine residues linked by dicarboxyl fatty acids. In general, the abundance profiles of the different derivatives in the five cultivars mimicked that of vicine and convicine, but some showed a derivative-specific profile. The description of the (con)vicine diversity will impact the interpretation of future studies on the biosynthesis of (con)vicine, and the content in potentially bio-active alkaloids in faba beans may be higher than that represented by the quantification of vicine and convicine alone. [ABSTRACT FROM AUTHOR]

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders. [ABSTRACT FROM AUTHOR]

Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC–MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using n-butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC–MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin. [ABSTRACT FROM AUTHOR]

FAF1 (FAS-associated factor 1) is involved in the activation of Fas cell surface death receptors and plays a role in apoptosis and necrosis. In patients with Parkinson's disease, FAF1 is overexpressed in dopaminergic neurons in the substantia nigra. KM-819, an FAF1 inhibitor, has shown potential for preventing dopaminergic neuronal cell death, promoting the degradation of α-synuclein and preventing its accumulation. This study aimed to develop and validate a quantitative analytical method for determining KM-819 levels in rat plasma using liquid chromatography–tandem mass spectrometry. This method was then applied to pharmacokinetic (PK) studies in rats. The metabolic stability of KM-819 was assessed in rat, dog, and human hepatocytes. In vitro metabolite identification and metabolic pathways were investigated in rat, dog, and human hepatocytes. The structural analog of KM-819, namely N-[1-(4-bromobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-2-(phenylsulfanyl) acetamide, served as the internal standard (IS). Proteins were precipitated from plasma samples using acetonitrile. Analysis was carried out using a reverse-phase C18 column with a mobile phase consisting of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile. The analytical method developed for KM-819 exhibited linearity within the concentration range of 0.002–10 μg/mL in rat plasma. The precision and accuracy of the intra- and inter-day measurements were <15% for the lower limit of quantification (LLOQ) and all quality control samples. KM-819 demonstrated stability under various sample storage conditions (6 h at room temperature (25 °C), four weeks at −20 °C, three freeze-thaw cycles, and pretreated samples in the autosampler). The matrix effect and dilution integrity met the criteria set by the Food and Drug Administration and the European Medicines Agency. This sensitive, rapid, and reliable analytical method was successfully applied in pharmacokinetic studies in rats. Pharmacokinetic analysis revealed the dose-independent kinetics of KM-819 at 0.5–5 mg/kg, with a moderate oral bioavailability of ~20% in rats. The metabolic stability of KM-819 was also found to be moderate in rat, dog, and human hepatocytes. Metabolite identification in rat, dog, and human hepatocytes resulted in the discovery of six, six, and eight metabolites, respectively. Glucuronidation and mono-oxidation have been proposed as the major metabolic pathways. Overall, these findings contribute to a better understanding of the pharmacokinetic characteristics of KM-819, thereby aiding future clinical studies. [ABSTRACT FROM AUTHOR]

Kratom leaves, consumed by millions worldwide as tea or ground leaf powder, contain multiple alkaloids, with mitragynine being the most abundant and responsible for most effects. Mitragynine is a partial µ-opioid receptor agonist and competitive antagonist at κ- and δ-opioid receptors; however, unlike morphine, it does not activate the β-arrestin-2 respiratory depression pathway. Due to few human mitragynine data, the largest randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of 500–4000 mg dried kratom leaf powder (6.65–53.2 mg mitragynine) was conducted. LC-MS/MS mitragynine and 7-hydroxymitragynine plasma concentrations were obtained after single and 15 daily doses. Mitragynine and 7-hydroxymitragynine Cmax increased dose proportionally, and AUC was slightly more than dose proportional. The median mitragynine Tmax was 1.0–1.3 h after single and 1.0–1.7 h after multiple doses; for 7-hydroxymitragynine Tmax, it was 1.2–1.8 h and 1.3–2.0 h. Steady-state mitragynine concentrations were reached in 8–9 days and 7-hydroxymitragynine within 7 days. The highest mean mitragynine T1/2 was 43.4 h after one and 67.9 h after multiple doses, and, for 7-hydroxymitragynine, it was 4.7 and 24.7 h. The mean 7-hydroxy-mitragynine/mitragynine concentration ratios were 0.20–0.31 after a single dose and decreased (0.15–0.21) after multiple doses. These mitragynine and 7-hydroxymitragynine data provide guidance for future clinical kratom dosing studies and an interpretation of clinical and forensic mitragynine and 7-hydroxymitragynine concentrations. [ABSTRACT FROM AUTHOR]

A method was developed for the determination of 26 drugs of abuse from different classes, including illicit drugs in quantitative dried blood spots (qDBSs), with the aim to provide a convenient method for drug testing by using only 10 μL of capillary blood. A satisfactory limit of quantification (LOQ) of 2.5 ng/mL for 9 of the compounds and 5 ng/mL for 17 of the compounds and a limit of detection (LOD) of 0.75 ng/mL for 9 of the compounds and 1.5 ng/mL for 17 of the compounds were achieved for all analytes. Reversed-phase liquid chromatography was applied on a C18 column coupled to MS, providing selective detections with both +ESI and -ESI modes. Extraction from the qDBS was performed using AcN-MeOH, 1:1 (v/v), with recovery ranging from 84.6% to 106%, while no significant effect of the hematocrit was observed. The studied drugs of abuse were found to be stable over five days under three different storage conditions (at ambient temperature 21 °C, at −20 °C, and at 35 °C), thus offering a highly attractive approach for drug screening by minimally invasive sampling for individuals that could find application in forensic toxicology analysis. [ABSTRACT FROM AUTHOR]

Employing naturally extracted dyes and their derivatives as photosensitizers towards the construction of dye-sensitized solar cells (DSSCs) has been recently emerging for establishing sustainable energy conversion devices. In this present work, Rhodobacter Sphaeroides Photobacteria (Rh. Sphaeroides) was used as a natural source from which Bacteriopheophytine-a (Bhcl) dye was extracted. Further, two cationic derivatives of Bhcl, viz., Guanidino-bacteriopheophorbide-a (Gua-Bhcl) and (2-aminoethyl)triphenylphosphono-bacteriopheophorbide-a (2AETPPh-Bhcl) were synthesized. The thus obtained Bhcl, Gua-Bhcl and 2AETPPh-Bhcl were characterized using liquid chromatography–mass spectrometry (LC–MS) and their photophysical properties were investigated using excitation and emission studies. All three near-infrared (NIR) responsive dyes were employed as natural sensitizers towards the construction of DSSC devices, using platinum as a photocathode, dye-sensitized P25-TiO2 as a photoanode and I−/I3− as an electrolyte. DSSCs fabricated using all three dyes have shown reasonably good photovoltaic performance, among which 2AETPPh-Bhcl dye has shown a relatively higher power conversion efficiency (η) of 0.38% with a short circuit photocurrent density (JSC) of 1.03 mA cm−2. This could be attributed to the dye's natural optimal light absorption in the visible and NIR region and uniform dispersion through the electrostatic interaction of the cationic derivatives on the TiO2 photoanode. Furthermore, the atomic force microscopy studies and electrochemical investigations using cyclic voltammetry, electrochemical impedance spectroscopy and Bode's plot also supported the enhancement in performance attained with 2AETPPh-Bhcl dye. [ABSTRACT FROM AUTHOR]

The high concentration of antibiotics in aquatic environments is a serious environmental issue. In response, researchers have explored photocatalytic degradation as a potential solution. Through chemical vapor deposition (CVD), we synthesized copper selenide (β-Cu2−xSe) and found it an effective catalyst for degrading tetracycline hydrochloride (TC-HCl). The catalyst demonstrated an impressive degradation efficiency of approximately 98% and a reaction rate constant of 3.14 × 10−2 min−1. Its layered structure, which exposes reactive sites, contributes to excellent stability, interfacial charge transfer efficiency, and visible light absorption capacity. Our investigations confirmed that the principal active species produced by the catalyst comprises O2− radicals, which we verified through trapping experiments and electron paramagnetic resonance (EPR). We also verified the TC-HCl degradation mechanism using high-performance liquid chromatography–mass spectrometry (LC-MS). Our results provide valuable insights into developing the β-Cu2−xSe catalyst using CVD and its potential applications in environmental remediation. [ABSTRACT FROM AUTHOR]

Cenobamate (CNB) is a new anti-seizure medication (ASM) recently introduced in clinical practice after approval by the FDA and EMA for the add-on treatment of focal onset seizures in adult patients. Although its mechanism of action has not been fully understood, CNB showed promising clinical efficacy in patients treated with concomitant ASMs. The accessibility of CNB could pave a way for the treatment of refractory or drug-resistant epilepsies, which still affect at least one-third of the patients under pharmacological treatment. In this context, therapeutic drug monitoring (TDM) offers a massive opportunity for better management of epileptic patients, especially those undergoing combined therapy. Here, we describe the first fully validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method for the quantification of CNB and concomitant ASMs in human plasma, with samples extracted either manually or by means of a liquid handler. Our method was validated according to the most recent ICH International Guideline M10 for Bioanalytical Method Validation and Study Sample Analysis. The method proved to be selective for CNB and displayed a linear range from 0.8 to 80 mg/L; no matrix effect was found (98.2 ± 4.1%), while intra-day and inter-day accuracy and precision were within the acceptance range. Also, CNB short- and long-term stability in plasma under different conditions was assessed. Leftover human plasma samples were employed as study samples for method validation. Our method proved to be highly sensitive and selective to quantify CNB and concomitant ASMs in human plasma; therefore, this method can be employed for a routinely TDM-based approach to support physicians in the management of an epileptic patient. [ABSTRACT FROM AUTHOR]