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Per- and polyfluoroalkyl substances (PFAS) are anthropogenic fluorine-containing compounds largely used in industrial and consumer applications. They tend to bioaccumulate in the human body after intake from various sources in daily life. Following repeated exposure to PFAS, a broad range of adverse health outcomes has been reported. Consequently, monitoring PFAS levels in human blood is of paramount importance for public health policies. In contrast with traditional venipuncture, dried blood spots (DBS) constitute a reliable, cheap, and less invasive technique to allow microsampling by capillary blood collected on a specific device. This work aimed to develop and validate an innovative analytical method, combining quantitative DBS with UHPLC-MS/MS instrumentation to identify and quantify 25 PFAS. The extraction procedure was developed and optimized within the range 2–100 ng/mL. Specifically, fortified blood was applied on Capitainer®B devices providing 10 μL of blood volume through a microfluidic channel. After 3 h of drying, the extraction was performed by methanol under sonication, followed by centrifugation. Then, the extraction solvent was evaporated; the residue was reconstituted with the mobile phase solution. The validated method evidenced good sensitivity, with limits of detection ranging from 0.4 ng/mL (PFODA, PFOS) to 1.0 ng/mL (PFOA, 3,6-OPFHpA). The ± 20% acceptability criteria established for intra- and inter-day precision and accuracy were fulfilled for all analytes. High recovery—above 80%—was recorded, whereas significant matrix effect resulted in ion enhancement (> 50%) for 13 analytes. In conclusion, the proposed workflow proved to be reliable, fit for purpose, and easily adaptable in the laboratory routine. [ABSTRACT FROM AUTHOR]

AbstractMethaqualone, introduced in the 1960s as a sedative-hypnotic alternative to barbiturates, was withdrawn from the market due to its side effects and growing recreational use. Despite this, interest in methaqualone and its analogs remains high, raising concerns about potential abuse in the future.An ultra-high-performance liquid chromatography method coupled with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) was developed to determine nine methaqualone-related compounds simultaneously. Biological samples were prepared using liquid-liquid extraction with ethyl acetate at pH 9, quantification was performed in blood using multiple reaction monitoring (MRM) mode. Methaqualone-d7 served as an internal standard. The limit of quantification (LOQ) ranged from 0.1 to 0.2 ng/mL, with precision and accuracy within 20%. Recovery ranged from 84.2% to 113.7%.The developed method allowed chromatographic separation of all compounds tested, including two structural isomers: methtylmethaqualone and etaqualone. The mass spectra aquired from quadrupole time-of-flight mass spectrometer allowed for the elucidation of comprehensive fragmentation study of methaqualone derivatives.The described situation poses a significant problem from the analytical point of view, as well as interpretation and forensic toxicological expertise. The developed method will contribute to increased analytical capabilities and enhanced detection of compounds from the methaqualone group that may appear on the illicit market. [ABSTRACT FROM AUTHOR]

For more than two millennia, Ferulago species have been revered as therapeutic herbs, maintaining their significance in present-day folk medicine practices. Therefore, the present study was conducted to investigate the phytochemical composition, inhibitory effects on metabolic enzymes, and possible therapeutic applications of F. trachycarpa, specifically focusing on its efficacy in diabetes management, anticholinergic effects, and antioxidant capabilities. The current investigation comprised an evaluation of a range of extracts acquired via conventional and modern methodologies, such as soxhlet (SOX), maceration (MAC) accelerated solvent extraction (ASE), homogenizer-assisted extraction (HAE), supercritical fluid extraction (SFE), microwave-assisted extraction (MW), and ultrasound-assisted extraction (UAE). Various techniques were employed to assess their antioxidant capacity and enzyme inhibition. Furthermore, the research utilized ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) to ascertain the principal phenolic compounds that are responsible for the antioxidant capacity observed in the various F. trachycarpa extracts. Among these, extracts from HAE, ASE, and MW revealed the most promise across all methodologies tested for their antioxidant potential. Furthermore, SFE and MAC extracts inhibited the most enzymes, including cholinesterases, tyrosinase, α -amylase, and α -glycosidase, indicating their potential as efficient natural treatments for several health-related issues. [ABSTRACT FROM AUTHOR]

Yogurt, a milk-derived product, is susceptible to mycotoxin contamination. While various methods have been developed for the analysis of dairy products, only a few have been specifically validated for yogurt. In addition, these methods are primarily focus on detecting aflatoxins and zearalenone. This study aimed to conduct a preliminary investigation into the presence of regulated, emerging, and modified mycotoxins in natural and oat yogurts available in the Spanish market. For this, a QuEChERS-based extraction method was optimized and then validated to detect and quantify 32 mycotoxins using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The method was in-house validated for the analysis of natural and oat yogurt in terms of linearity, matrix effect, sensitivity, accuracy, and precision. Satisfactory performance characteristics were achieved; for most of the analytes, LOQs were lower than 2 ng/g, and recoveries ranged from 60 to 110% with a precision, expressed as the relative standard deviation of the recovery, lower than 15%. Subsequently, the validated method was applied to analyze commercial yogurt samples, revealing a notable incidence of beauvericin and enniatins, with some analogues found in up to 100% of the samples. Alternariol methyl ether was also frequently found, appearing in 50% of the samples. Additionally, the study identified regulated toxins such as fumonisins, ochratoxin A , and HT-2 toxin. These results provide new incidence data in yogurt, raising concerns about potential health risks for consumers. [ABSTRACT FROM AUTHOR]

This study established novel and high-throughput strategies for the simultaneous analysis of 30 fluorinated emerging pollutants in different matrices from the shrimp aquaculture system in eastern China using UHPLC-MS/MS. The parameters of SPE for analysis of water samples and of QuEChERS methods for sediment and shrimp samples were optimized to allow the simultaneous detection and quantitation of 17 per- and polyfluoroalkyl substances (PFASs) and 13 fluoroquinolones (FQs). Under the optimal conditions, the limits of detection of 30 pollutants for water, sediment, and shrimp samples were 0.01–0.30 ng/L, 0.01–0.22 μg/kg, and 0.01–0.23 μg/kg, respectively, while the limits of quantification were 0.04–1.00 ng/L, 0.03–0.73 μg/kg, and 0.03–0.76 μg/kg, with satisfactory recoveries and intra-day precision. The developed methods were successfully applied to the analysis of multiple samples collected from aquaculture ponds in eastern China. PFASs were detected in all samples with concentration ranges of 0.18–0.77 μg/L in water, 0.13–1.41 μg/kg (dry weight) in sediment, and 0.09–0.96 μg/kg (wet weight) in shrimp, respectively. Only two FQs, ciprofloxacin and enrofloxacin, were found in the sediment and shrimp. In general, this study provides valuable insights into the prevalence of fluorinated emerging contaminants, assisting in the monitoring and control of emerging contaminants in aquatic foods. [ABSTRACT FROM AUTHOR]

Edible Insects (EIs) are an alternative source of bioactive compounds such as proteins or fatty acids and micronutrients as vitamins or minerals, thus showing potential to replace traditional foodstuffs in an economical and environmentally friendly way. Nonetheless, EIs can accumulate hazardous chemicals such as mycotoxins and heavy metals. The aim of the present study is to determine mycotoxins and heavy metal content in raw insect samples and those resulting products obtained after supercritical fluid extraction (SFE). Insect samples included Acheta domesticus (cricket) meal, Tenebrio molitor (mealworm) meal, Alphitobius diaperinus (buffalo worm), and Locusta migratoria (locust). For this purpose, a QuEChERS method followed by LC-MS/MS analysis was optimized with good results for the analysis of mycotoxins, principally Aflatoxins (AFs), Ochratoxin A (OTA), and Enniatins (ENNs). In contrast, heavy metals (As, Cd, Hg, Pb) were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The results obtained revealed that Locust was positive for AFG2 at a level of 115.5 μg/kg, and mealworm was only contaminated with OTA at 58.1 μg/kg. Emerging mycotoxins (ENNA, ENNA1, ENNB, and ENNB1) were detected at lower levels < 2.2 µg/Kg. Concerning heavy metals, limits exceeding regulation were detected for Cd in the insect species studied, with levels up to 219 μg/kg, and for Pb in crickets (100.3 μg/kg). Finally, the analysis of the post-extraction solids after SFE processing revealed that heavy metals remained in the resulting SFE cakes, while mycotoxins were detected at negligible levels (up to 1.3 µg/Kg). [ABSTRACT FROM AUTHOR]

Background and Objectives: Dovitinib (DVB) is a pan-tyrosine kinase inhibitor (TKI) that can be administered orally. In September 2023, the FDA granted Oncoheroes approval to proceed with an Investigational New Drug (IND) application for dovitinib. This application is intended for the treatment of relapsed or advanced juvenile solid tumors, namely, osteosarcoma. Materials and Methods: The target of the present study was to develop a rapid, green, accurate, and sensitive UHPLC-MS/MS method for measuring DVB levels in human liver microsomes (HLMs). The validations of the HLMs were performed via the established UHPLC-MS/MS approach, as stated in the US FDA reported guidelines for the standards of bioanalytical method validation protocol. The StarDrop in silico software package (version 6.6), which involves the DEREK and WhichP450 in silico modules, was used to check the DVB structure for hazardous alerts and metabolic instability. The DVB and encorafenib (EFB), internal standard, and chromatographic peaks were successfully separated using a reversed phase column (an Eclipse Plus Agilent C8 column) and an isocratic mobile phase. The production of DVB parent ions was accomplished by utilizing the positive ionization mode of an ESI source. The identification and measurement of DVB daughter ions were conducted using the MRM mode. Results: The inter-day accuracy and precision exhibited a spectrum of values in the range of −0.56% to 9.33%, while the intra-day accuracy and precision showcased a range of scores between 0.28% and 7.28%. The DVB calibration curve showed a linear relationship that ranged from 1 to 3000 ng/mL. The usefulness of the currently validated UHPLC-MS/MS method was approved by the lower limit of quantification (LLOQ) of 1 ng/mL. The AGREE findings demonstrate that the UHPLC-MS/MS method had a noteworthy degree of ecological greenness. The in vitro half-life (t1/2) and intrinsic clearance (Clint) of DVB were calculated to be 15.48 min and 52.39 mL/min/kg, respectively, which aligned with the findings from the WhichP450 software (version 6.6). Conclusions: Via the usage of in silico software, it has been observed that making small changes to the structure of the aryl piperazine ring and quinolinone moieties, or replacing these groups in the drug design process, shows potential for enhancing the metabolic safety and stability of newly developed derivatives compared to DVB. [ABSTRACT FROM AUTHOR]

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External contamination of hair by cannabis smoking requires a careful evaluation in forensic toxicology. Medical and recreational cannabis are increasingly consumed by e‐cigarettes, which give rise to side‐stream vapor. Moreover, products containing low Δ9‐tetrahydrocannabinol (Δ9‐THC) and rich in cannabidiol (CBD) started spreading legally. The goal of the present study was to assess whether hair analysis could allow to distinguish the type of delivered product, with low or high Δ9‐THC, and the delivering mode, by smoking or vaping. Contamination of blank hair was mimicked by in vitro exposure to low‐ (0.4%) and high‐Δ9‐THC (9.7%) products delivered by smoking and vaping within a small confined system. Cannabis vaping extracts were prepared to deliver identical target Δ9‐THC doses. Eighty samples were analyzed by ultrahigh‐performance liquid chromatography mass spectrometry and quantified for Δ9‐THC and CBD. After contamination by cannabis smoking, THC levels were in line with past in vitro and in vivo studies. Samples exposed to cannabis (169.30 ng/mg) showed significantly higher Δ9‐THC than hair exposed to "light cannabis" (35.54 ng/mg), and the opposite was seen for the CBD/Δ9‐THC ratio. Hair contaminated by vaping or smoking did not show a statistically different Δ9‐THC content. Under our in vitro conditions, hair analysis might allow to discriminate whether external contamination is determined by products containing low or high Δ9‐THC, but not the delivering mode. More research is needed in real‐life conditions, to see whether the same also applies to the interpretation of forensic casework. [ABSTRACT FROM AUTHOR]

Introduction: Semen Cuscutae is a traditional Chinesemedicine (TCM) that tonifies the kidneys and preventsmiscarriage. According to Chinese medicine theory, kidney deficiency is one of the main causes of recurrent spontaneous abortion (RSA). The previous studies showed that raw product of Semen Cuscutae (SP) and Semen Cuscutae processed with salt solution (YP) have ameliorative effects on RSA, and that YP is superior to SP.However, the active components of YP to ameliorate RSA remain unclear and require further studies. The objective of this study is to investigate the active components of YP in ameliorating RSA. Methods: First, a rat model of RSA was established using hydroxyurea in combination with mifepristone. Aqueous decoction of YP was given by gavage to rats. Second, pregnant rats were sampled on days 5, 7, 9, 10 and 12 during the modelling period. The content of Hyperin (HY), astragalin (AS) and kaempferol-3-O-ß-D-glucuronide (KA) in blood and liver, heart, spleen, lung and kidney tissues were detected by liquid chromatography-mass spectrometry (LC-MS). The pharmacodynamic indicators including progesterone (P), chorionic gonadotropin ß (ß-HCG), estradiol (E2), tumor necrosis factor-a (TFN-a), interleukin 4 (IL-4), and tryptophan (TRP) were measured by enzyme-linked immunosorbent assay (ELISA) Pearson's correlation analysis and grey relational analysis were used to establish the relationship between the pharmacodynamic indexes and chemical constituents. Results: The pharmacokinetic results showed that the area under curve (AUC) value of KA was the largest. The tissue distribution results showed that astragalin was widely distributed in liver, heart, spleen, lung and kidney in the RSA model rats, while HY was detected only in the uterus, and KA was detected only in the kidney. The pearson correlationl analysis showed that KA was significantly and positively correlated with the contents of E2, P, ß-HCG and TRP. Both AS and HY were significantly negatively correlated with the content of TNF-a, respectively. Discussion: This study reveals the pharmacokinetics and tissue distribution of KA, AS and HY in rats with RSA. It was elucidated that all three were involved in the regulation of progesterone levels and immune function. It initially revealed the mechanism of action of YP in enhancing the improvement of RSA, and it provided a theoretical basis for the quality assessment of YP. [ABSTRACT FROM AUTHOR]

Practical Application Fermentation is critical for producing high‐quality cocoa, yet its kinetics and resulting chemical and sensory outcomes are poorly understood and thus difficult to manage. Cocoa sweatings (CS), the liquid runoff produced early during fermentation and typically drained off, may beneficially affect fermentation outcome when added back into the fermenting mass. Here, we report how back‐addition of CS affects composition and sensory perception of roasted cocoa liquor after 5, 6, and 7 days of fermentation. Cocoa liquor (= 100% chocolate) made from beans fermented for 5 days with the addition of CS were similar in sensory perception to those fermented for 7 days without added CS. Twenty‐one flavor compounds showed similar patterns to the sensory results: In the beans fermented with CS, these compounds remained at similar levels after 5, 6, and 7 days of fermentation, while the same compounds significantly changed in the samples fermented conventionally, without CS addition. These results suggest a link between changes in flavor composition and sensory differences in roasted cocoa. Future work is needed to reveal the mechanism of flavor stabilization throughout fermentation resulting from the back‐addition of CS.Roasted cocoa liquor fermented with cocoa sweating (CS) is sensorily similar when fermented for 5 or 7 days and produces cocoa that is sensorily similar to traditionally fermented cocoa in shorter time (5 days vs. 7 days). The addition of CS seems to stabilize 21 flavor compounds throughout fermentation mimicking changes in sensory perception. The back‐addition of CS could help standardize cocoa fermentation as indicated by more consistent temperature evolution. [ABSTRACT FROM AUTHOR]

Oat products have gained widespread recognition as a health food due to their rich and balanced nutritional profile and convenience. However, the unique matrix composition of oats, which differs significantly from other cereals, presents specific challenges for mycotoxin analysis. This study presents an ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method enhanced with an innovative egg white gel pretreatment for the simultaneous analysis of 13 regulated and unregulated trichothecenes in oats. The method demonstrated excellent performance with high accuracy (> 87.5%), repeatability (< 5.7%), and reproducibility (< 8.1%). Analysis of 100 commercial oat products revealed a concerning detection rate (78%) for at least one of the 11 trichothecenes investigated. Notably, deoxynivalenol, exceeding the standard limit in 2% of samples, exhibited the highest detection rate (62%). Additionally, concerning co-occurrence patterns and positive correlations were observed, highlighting potential synergistic effects. The first-time detection of unregulated mycotoxins (T-2 triol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, and neosolaniol) underscores the need for comprehensive monitoring. This method, while developed for oats, shows potential for broader application to other cereals, though further investigation and confirmation are necessary. These findings suggest a potentially underestimated risk of trichothecenes in oats, necessitating continuous monitoring to ensure consumer safety. [ABSTRACT FROM AUTHOR]

Post‐replicative DNA N6‐methyladenine (pr6mdA) can form via bona fide methylase‐catalyzed adenine methylation, playing a pivotal role in embryonic development and other biological processes. Surprisingly, pre‐methylated adenine can be erroneously incorporated into DNA as misincorporated N6‐methyladenine (i6mdA) via DNA polymerase‐mediated replication. Despite pr6mdA and i6mdA sharing identical chemical structures, their biological functions diverge significantly, presenting a substantial challenge in distinguishing between the two. Here, for the first‐time, it is exploited that the adenosine deaminase‐like (Adal) protein and a corresponding activity‐null mutant to construct an Adal lentivirus toolkit. With this newly designed toolkit, both pr6mdA and i6mdA can be identified and quantified simultaneously. The presence of 6mdA in the bone marrow cells of mice is shown, with its levels serving as indicators for growth with age, probably reflecting the cellular stress‐caused changes in RNA decay, nucleotide pool sanitation, and transcription. Collectively, a powerful toolkit to advance understanding of both pr6mdA and i6mdA is demonstrated. [ABSTRACT FROM AUTHOR]

The fungicide pyraclostrobin is the main measure used to control apple alternaria blotch in production. To evaluate the potential dietary risks for consumers, the dissipation and terminal residues of pyraclostrobin were investigated using ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS/MS). Pyraclostrobin in apples was extracted by acetonitrile with 2% ammonia and then purified using primary secondary amine (PSA) and graphitized carbon black (GCB). The method showed good linearity within the concentration range of 0.005–0.1 mg L−1, with a coefficient of determination (R2) ≥ 0.9958. The recoveries ranged from 96.0% to 103.8%, with relative standard deviations (RSDs) between 0.8% and 2.3%. The limit of quantification (LOQ) was 0.01 mg kg−1. Pyraclostrobin dispersible oil suspension was applied in 12 apple fields across China according to good agricultural practices (GAPs). In Beijing and Shandong, the dissipation of pyraclostrobin followed first-order kinetic equations, with a half-life of 11 days. The terminal residues ranged from <0.01 to 0.09 mg kg−1. The national estimated daily intake (NEDI) of pyraclostrobin was compared with the acceptable daily intake (ADI), resulting in risk quotient (RQc) of 80.8%. These results suggest that pyraclostrobin poses a low health risk to consumers under GAP conditions and according to recommended dosages. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration–time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity. [ABSTRACT FROM AUTHOR]

Enramycin, a common growth promoter utilized in chickens and pigs, is sensitive against Gram-positive bacteria, and the maximum residue limit (MRL) of enramycin set up by is 30 µg/kg. However, the methods have been reported for detecting enramycin have failed to meet the accuracy requirements, with the required limit of quantification being higher than the MRL. To address this issue, we developed a high-sensitive and robust analytical method based on ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS), to determine enramycin residues in swine tissues, including liver, kidney, pork, and fat. The ENV cartridge was selected to cleanup and enrich analytes after being extracted using a mixture of 55% methanol containing 0.2 M hydrochloric acid. With comprehensively validation, this established method was found great linearity of enramycin in each tissue, with a coefficient of variation above 0.99. Satisfactory recoveries from four different spiking levels were acquired (70.99-101.40%) while the relative standard deviations were all below 9%. The limit of quantification of enramycin in the present study is 5 µg/kg in fat and 10 µg/kg in other tissues, meeting the requirements for conducting the corresponding safety evaluation study. This method was demonstrated with excellent specificity, stability, and high sensitivity. To conclude, this novel approach is sufficiently sensitive and robust for the safety evaluation of enramycin in food products. [ABSTRACT FROM AUTHOR]

This study aimed to provide novel information on the impact of indigenous non-Saccharomyces yeasts, including Metschnikowia chrysoperlae, Metschnikowia sinensis/shanxiensis, Metschnikowia pulcherrima, Lachancea thermotolerans, Hanseniaspora uvarum, Hanseniaspora guilliermondii, and Pichia kluyveri, on metabolites related to the metabolism of tryptophan, phenylalanine, and tyrosine. The experiment included two fermentation practices: monoculture and sequential fermentation with commercial Saccharomyces cerevisiae, using sterile Maraština grape juice. A targeted approach through ultrahigh-resolution liquid chromatography associated with mass spectrometry was used to quantify 38 metabolites. All the indigenous yeasts demonstrated better consumption of tryptophan in monoculture than in interaction with S. cerevisiae. M. sinensis/shanxiensis was the only producer of indole-3-carboxylic acid, while its ethyl ester was detected in monoculture fermentation with H. guilliermondii. H. guilliermondii consumed the most phenylalanine among the other isolates. 5-hydroxy-L-tryptophan was detected in fermentations with M. pulcherrima and M. sinensis/shanxiensis. M. pulcherrima significantly increased tryptophol content and utilised tyrosine in monoculture fermentations. Sequential fermentation with M. sinensis/shanxiensis and S. cerevisiae produced higher amounts of N-acetyl derivatives of tryptophan and phenylalanine, while H. guilliermondii-S. cerevisiae fermentation resulted in wines with the highest concentrations of L-kynurenine and 3-hydroxyanthranilic acid. P. kluyveri produced the highest concentration of N-acetyl-L-tyrosine in monoculture fermentations. These findings highlight the different yeast metabolic pathways. [ABSTRACT FROM AUTHOR]

Given the increasing concern about chemical exposure from textiles, our study examines the risks of dermal exposure to bisphenol A (BPA), bisphenol S (BPS), bisphenol B (BPB) and bisphenol F (BPF) from conventional and recycled textiles for adults, aiming to obtain new data, assess exposure, and evaluate the impact of washing on bisphenol levels. A total of 57 textile samples (33 from recycled and 24 from conventional material) were subjected to ultrasound-assisted extraction (UAE) followed by ultra-high performance liquid chromatography with tandem mass spectrometry analysis (UHPLC-MS/MS). The BPA and BPS concentrations varied widely (BPA: < 0.050 to 625 ng/g, BPS: 0.277–2,474 ng/g). The median BPA content in recycled textiles (13.5 ng/g) was almost twice as high as that of 7.66 ng/g in conventional textiles. BPS showed a median of 1.85 ng/g in recycled textiles and 3.42 ng/g in conventional textiles, indicating a shift from BPA to BPS in manufacturing practices. Simulated laundry experiments showed an overall reduction in bisphenols concentrations after washing. The study also assessed potential health implications via dermal exposure to dry and sweat-wet textiles compared to a tolerable daily intake (TDI) of 0.2 ng/kg bw/day for BPA set by the European Food Safety Authority (EFSA). Exposure from dry textiles remained below this threshold, while exposure from wet textiles often exceeded it, indicating an increased risk under conditions that simulate sweating or humidity. By finding the widespread presence of bisphenols in textiles, our study emphasises the importance of being aware of the potential risks associated with recycling materials as well as the benefits. [ABSTRACT FROM AUTHOR]

This study aimed to utilize ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to analyze and quantify eight therapeutic components in Paeonia lactiflora and Glycyrrhiza decoction. The goal was to establish an accurate, efficient, and applicable method for determining the composition of this formula, providing a reference for its clinical application. Methanol was employed to extract the therapeutic components from Paeonia lactiflora and Glycyrrhiza decoction, forming the test sample solution. UHPLC-MS/MS technology was applied to separate and analyze the test samples. The results indicated that upon analysis, the eight reference standards exhibited excellent linear relationships, and the test samples remained stable within 24 h. The content of paeoniflorin, paeonolide, glycyrrhizic acid A, quercetin, chebulic acid, liquiritin, naringenin, and glycyrrhetic acid was determined to be 3.530 ± 0.124, 0.139 ± 0.006, 0.245 ± 0.008, 0.779 ± 0.026, 0.433 ± 0.021, 0.388 ± 0.018, 0.617 ± 0.013, and 0.081 ± 0.005 mg/mL, respectively. This study established that UHPLC-MS/MS analysis demonstrated high efficiency and broad applicability, reflecting the chemical composition characteristics of Paeonia lactiflora and Glycyrrhiza decoction. This research provided a quantitative analysis method for the eight therapeutic components in Paeonia lactiflora and Glycyrrhiza decoction, applicable to its clinical use and quality control. [ABSTRACT FROM AUTHOR]

Helianthemum nummularium (HN) and Helianthemum oelanticum subsp. incanum (HO) are plant species, among Cistaceae, that are highly distributed in the Mediterranean region. In the current study, extracts of the aerial parts from both species have been analyzed phytochemically. The non-polar extract analysis resulted in the identification of 15 compounds in each species, mainly terpene and fatty acid derivatives, through GC–MS. The methanolic extract analysis, conducted through UHPLC–MS/MS, led to the identification of 39 metabolites in HN and 29 in HO, respectively, the majority of which were phenolics. Among the identified compounds, several have also been isolated and structurally determined (from HN: rutin, linoleic acid, gallic acid, and isoquercetin, and from HO: quercetin-3-O-(2″-O-galloyl)-galactopyranoside, methyl gallate, catechin-3-O-glucopyranoside, and astragalin, while hyperoside, and cis- and trans-tiliroside have been determined in both species). Furthermore, the methanolic extracts of HN and HO displayed a high total phenolic content (177.2 mg GA/g extract and 150.6 mg GA/g extract, respectively) and considerable free-radical scavenging activity against the DPPH radical (94.6% and 94.0% DPPH inhibition, respectively). Antimicrobial testing showed stronger inhibition of HN against Gram (+) bacterial strains (MIC values 0.07–0.15 mg/mL), while both extracts exhibited low tyrosinase-inhibitory activity. Considering the lack of studies conducted on the chemistry and biological activities of the genus Helianthemum, the chemical characterization of extracts could contribute to new sources of bioactive metabolites to be explored and exploited for further potential applications such as food and/ or the cosmetic industry. [ABSTRACT FROM AUTHOR]

To explore potential factors contributing to high fluoroquinolone resistance levels, it is essential to develop analytical methods capable of detecting residues and trace amounts of antibiotic use in broilers. The aim of the present study was to develop and in-house validate a sensitive UHPLC-MS/MS method capable of determining enrofloxacin (ENR) and flumequine (FLU) residues at slaughter age (day 45) when the animals were treated with these antimicrobials one day after hatching. Residue depletion of ENR and FLU in feathers was also assessed. Two experimental trials were performed, both consisting of 5 different treatment groups. In the first trial animals were treated with ENR and in the second one with FLU. The developed method was successfully validated and was found to be sensitive enough to detect residues of fluoroquinolones in the feathers up until slaughter age in all treatment groups. Average ENR concentration on day 45 was 10 ng g−1 feather after drinking water treatment, with all concentrations above the limit of quantification (LOQ) of 5 ng g−1 feather. For FLU average concentration on day 45 after drinking water administration was 4 ng g−1 feather, with an LOQ of 1 ng g−1 feather. Therefore, the method is suited for application to monitor fluoroquinolone use in broilers. [ABSTRACT FROM AUTHOR]

We established an efficient analytical approach for simultaneous determination of benthiavalicarb-isopropyl and its four metabolites (KIF-230-M1, KIF-230-M3, KIF-230-M4, and KIF-230-M5) in fruits and vegetables. Samples were extracted with acidified acetonitrile, with octadecylsilane and graphitised carbon black as sorbent for clean-up, and UHPLC-MS/MS for determination. The approach was determined at spikes of 5, 50, and 500 μg kg−1. The recoveries of the six matrices analyzed ranged from 74.5% to 115.6% with 0.5–12.6% for intra-day RSDr (n = 5), and 0.4–13.8% for inter-day RSDR (n = 15). The five analytes in all matrices achieved high linearity (R2 > 0.9917). The limit of quantification (LOQ) of benthiavalicarb-isopropyl as well as its four metabolites in all matrices was 5 μg kg−1. This analytical approach allows for monitoring residues of benthiavalicarb-isopropyl and its metabolites in vegetables and fruits. [ABSTRACT FROM AUTHOR]

Background: Ticagrelor is a novel oral antiplatelet agent which can selectively inhibit P2Y12 receptor. Bleeding and dyspnea are common adverse reactions of ticagrelor in clinic. The side effects of ticagrelor are correlated with the plasma concentration of ticagrelor. Objective: This study aimed to evaluate the catalytic characteristics of 22 CYP3A4 alleles identified in the Chinese Han population on the metabolism of ticagrelor in vitro, focusing on the effect of CYP3A4 polymorphism on ticagrelor metabolism. Methods: In this study, insect cells were used to express 22 CYP3A4 variants, which were then incubated with 1–50 µM ticagrelor at 37 °C for 30 minutes to obtain the metabolite (AR-C124910XX). AR-C124910XX was detected by UHPLC-MS/MS to calculate the kinetic parameters, including Km, Vmax and CLint. Results: Compared to the wild-type, most CYP3A4 alleles exhibited significant differences in intrinsic clearance. The intrinsic clearance of CYP3A4*11, *18 and *33 was much higher than that of wild-type; four variants exhibited similar intrinsic clearance values as the wild-type enzyme; The remaining 14 variants showed significantly reduced intrinsic clearance values, ranging from 1.48% to 75.11% of the wild-type; CYP3A4*30 displayed weak or no activity. Conclusion: This study conducted a comprehensive assessment of the effect of CYP3A4 variants on ticagrelor's metabolism. The results suggested that there is allele-specific activity towards ticagrelor in vitro. These findings can provide some insights and predictions for treatment strategies and risk assessments associated with ticagrelor in clinical practice. [ABSTRACT FROM AUTHOR]

Plants, including pumpkins (Cucurbita spp.), are an interesting source of nutrients and bioactives with various health benefits. In this research, carotenoid extracts obtained from the pulp of eight pumpkin varieties, belonging to the C. moschata and C. maxima species, were tested for cytotoxicity on SH-SY5Y neuroblastoma cells. The results showed that pumpkin bioactives exert a cytotoxic action against the tested cells, in particular Butternut extract at a 100 μM (53.69 μg/mL) concentration after 24 h of treatment and Mantovana extract at 50 μM (26.84 μg/mL) after 48 h. Moreover, the carotenoid extracts also showed interesting in vitro antioxidant activity, evaluated by ABTS and ORAC assays. To fully characterize the qualitative and quantitative profile of carotenoids in the tested extracts, a high-performance chromatographic technique was performed, revealing that pumpkin pulp carotenoids were mainly represented by β-carotene, mono- and di-esterified hydroxy- and epoxy-carotenoids. Moreover, the carotenoid dataset was also useful for discriminating samples from two different species. In conclusion, the results of the present study highlight the potential anti-cancer activity of pumpkin carotenoid extracts and the possibility of using them as chemotherapeutic adjuvants. [ABSTRACT FROM AUTHOR]

Multi-targeted tyrosine kinase inhibitor QLNC-3A6 Di-maleate, a structurally novel small molecule compound, has therapeutic efficacy for the treatment of canine cutaneous mast cell tumor (CMCT) caused by mutations in the c-Kit gene. Since pharmacokinetic (PK) information plays an important role in the development and application of new drugs, etc., a rapid, highly sensitive and selective UHPLC-MS/MS analytical method was developed and validated for the first time in this study for the quantitative detection of QLNC-3A6 in canine plasma. 100 µL of plasma was precipitated using 350 µL of acetonitrile, and Chromatographic separation was performed on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 µm) at a flow rate of 0.4 mL/min, the mobile phases were set to 0.1% formic acid aqueous solution (A) and 0.1% formic acid acetonitrile (B). The calibration curve linear range was 0.5–100 ng/mL (R2>0.99). The intraday and interday precision values (relative standard deviation, RSD) were 2.06–13.57% and 6.90–9.14%. Intraday and interday accuracies were −10.73 to 9.54% and −3.86 to 0.70% respectively. The dilution integrity RSD value and stability RSD value were less than 3.77 and 7.45%, respectively. Subsequently, the pharmacokinetics were investigated in canine after oral administration of QLNC-3A6 Di-maleate tablets at a dose of 3 mg/kg BW using this method. The results showed that QLNC-3A6 showed fast absorption rate, rapid distribution and slow metabolic elimination in canine plasma. The results of the main PK parameters including λz, T1/2λz, Cmax, Tmax and AUClast were 0.07 ± 0.01/h, 11.00 ± 2.57 h, 50.88 ± 31.94 ng/mL, 9.08 ± 11.57 h and 836.48 ± 230.53 ng h/mL, respectively.

Jinling Hou,1,&ast; Xiaoyan Wang,1,&ast; Jian Zhang,1 Zhuojun Shen,1 Xiang Li,2 Yuanxiao Yang2 1School of Pharmacy, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanxiao Yang; Xiang Li, Email yyx104475@163.com; leexiang2004@126.comBackground and Aim: Previous studies of our research group have shown that Chuanxiong Renshen Decoction (CRD) has the effect of treating AD, but the exact mechanism of its effect is still not clarified. The aim of this study was to investigate the effect and mechanism of CRD on AD neuroinflammation.Materials and Methods: Morris Water Maze (MWM) tests were employed to assess the memory and learning capacity of AD mice. HE and Nissl staining were used to observe the neural cells of mice. The expression of Iba-1 and CD86 were detected by immunohistochemical staining. Utilize UHPLC-MS/MS metabolomics techniques and the KEGG to analyze the metabolic pathways of CRD against AD. Lipopolysaccharide (LPS) induced BV2 microglia cells to construct a neuroinflammatory model. The expression of Iba-1 and CD86 were detected by immunofluorescence and flow cytometry. The contents of TNF-α and IL-1β were detected by ELISA. Western blot assay was used to detect the expression of PPARγ, p-NF-κB p65, NF-κB p65 proteins and inflammatory cytokines iNOS and COX-2 in PPARγ/NF-κB pathway with and without PPARγ inhibitor GW9662.Results: CRD ameliorated the learning and memory ability of 3×Tg-AD mice, repaired the damaged nerve cells in the hippocampus, reduced the area of Iba-1 and CD86 positive areas in both the hippocampus and cortex regions, as well as attenuated serum levels of IL-1β and TNF-α in mice. CRD-containing serum significantly decreased the expression level of Iba-1, significantly reduced the levels of TNF–α and IL-1β, significantly increased the protein expression of PPARγ, and significantly decreased the proteins expression of iNOS, COX-2 and p-NF-κB p65 in BV2 microglia cells. After addition of PPARγ inhibitor GW9662, the inhibitory effect of CRD-containing serum on NF-κB activation was significantly weakened.Conclusion: CRD can activate PPARγ, regulating PPARγ/NF-κB signaling pathway, inhibiting microglia over-activation and reducing AD neuroinflammation.Keywords: Alzheimer’disease, Chuanxiong Renshen Decoction, UHPLC-MS/MS, neuroinflammation, PPAR&#x03B3

Betaine is a useful compound that has various activities and is the marker compound of Lycium chinense fruit in Korean Pharmacopoeia. we seek to support the stable production of medicinal goji berries, which have significant potential in the pharmaceutical industry due to their high values, and to provide foundational data for consistent quality control. This study's purpose was to examine the correlation among betaine content, environmental variables, and the growth characteristics of L. chinense fruits. The fruits were collected from 25 cultivation sites across South Korea. We investigated five growth characteristics and betaine contents in L. chinense fruits and twelve soil physicochemical properties, and seven meteorological data at cultivation sites. The fruit's growth characteristics included a length of 15.62–26.49 mm, a width of 7.09–11.38 mm, a fresh weight of 0.73–1.62 g, and a sugar content of 11.10–19.62 Brix°. Its betaine content ranged from 0.54% to 0.97%. The betaine content was positively correlated with electrical conductivity (0.327 **), exchangeable potassium (0.314 **), and sodium (0.259 *) and negatively correlated with annual average minimum temperature (−0.256 *) and annual average temperature (−0.242 *). Also, betaine showed a positive correlation with the length of the fruit (0.294 *) and the fresh weight of the fruit (0.238 *). These results can be used to find the best cultivation method and to manage quality control for the highly economical L. chinense fruit. [ABSTRACT FROM AUTHOR]

This study investigates the current situation and possible health risks due to pharmaceutically active compounds (PhACs) including analgesics, antibiotics, antifungals, anti-inflammatories, psychiatric and cardiovascular drugs, and metabolites, in indoor environments. To achieve this objective, a total of 85 dust samples were collected in 2022 from three different Spanish indoor environments: homes, classrooms, and offices. The analytical method was validated meeting SANTE/2020/12830 and SANTE/12682/2019 performance criteria. All indoor dust samples except one presented at least one PhAC. Although concentration levels ranged from < LOQ to 18 µg/g, only acetaminophen, thiabendazole, clotrimazole, and anhydroerythromycin showed quantification frequencies (Qf %) above 19% with median concentrations of 166 ng/g, 74 ng/g, 25 ng/g and 14 ng/g, respectively. The PhAC distribution between dust deposited on the floor and settled on elevated (> 0.5 m) surfaces was assessed but no significant differences (p > 0.05, Mann–Whitney U-test) were found. However, concentrations quantified at the three types of locations showed significant differences (p < 0.05, Kruskal–Wallis H-test). Homes turned out to be the indoor environment with higher pharmaceutical concentrations, especially acetaminophen (678 ng/g, median). The use of these medicines and their subsequent removal from the body were identified as the main PhAC sources in indoor dust. Relationships between occupant habits, building characteristics, and/or medicine consumption and PhAC concentrations were studied. Finally, on account of concentration differences, estimated daily intakes (EDIs) for inhalation, ingestion and dermal adsorption exposure pathways were calculated for toddlers, adolescents and adults in homes, classrooms and offices separately. Results proved that dust ingestion is the main route of exposure, contributing more than 99% in all indoor environments. Moreover, PhAC intakes for all studied groups, at occupational locations (classrooms and offices) are much lower than that obtained for homes, where hazard indexes (HIs) obtained for acetaminophen (7%—12%) and clotrimazole (4%-7%) at the worst scenario (P95) highlight the need for continuous monitoring. [ABSTRACT FROM AUTHOR]

An automated flow analysis-solid phase extraction (FA-SPE) system and methodology of ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) analysis were developed for the determination of selected antiviral drugs (acyclovir, amantadine, rimantadine, and oseltamivir) in water samples. The proposed FA-SPE approach enables the integration of various extraction stages and elimination of the sample evaporation step and offers individual customisation of SPE parameters, inter alia sample, and eluate flow rate and volume. Using the developed FA-SPE procedure, e.g. a 100-fold preconcentration of the target analytes in 1 h was achieved. A method for chromatographic analysis was also developed to determine the selected antiviral drugs in combination with the use of the FA-SPE system. The developed FA-SPE UHPLC-MS/MS method was validated including the determination of linearity of analytical graphs, limits of detection (5.5–99.9 pg mL−1) and quantification (18.3–329.8 pg mL−1), intra-day (1.8–8.3%) and inter-day (3.0–9.2%) precision, recovery (95.6–105.3%), and matrix effects (− 12.9 to 13.2%). The proposed method was successfully applied to analyse tap, drinking, and river water samples, revealing the presence of amantadine at a concentration of 40.1 pg mL−1 in one sample. The environmental impact of the developed FA-SPE sample preparation procedure was also assessed using the AGREEprep metric tool and compared with five other literature methods, achieving the most sustainable outcome. [ABSTRACT FROM AUTHOR]

Palbociclib (Ibrance; Pfizer) was approved for the management of metastatic breast cancer characterized by hormone receptor‐positive/human epidermal growth factor receptor 2 negative status. The objective of this study was to create a fast, precise, environmentally friendly, and highly sensitive ultra‐high‐performance liquid chromatography‐tandem mass spectrometry approach for quantifying palbociclib (PAB) in human liver microsomes with the application for assessing metabolic stability. The validation features were performed in agreement with the bioanalytical method validation standards outlined by the US Food and Drug Administration. The StarDrop software (WhichP450 and DEREK modules) was used in screening the metabolic lability and structural alerts of PAB. The separation of PAB and encorafenib (as an internal standard) was achieved on a C8 column, employing an isocratic mobile phase. The inter‐day and intra‐day accuracy and precision ranged from ‐6.00% to 4.64% and from ‐2.33% to 3.13%, respectively. The constructed calibration curve displayed a linearity in the range of 1–3000 ng/mL. The sensitivity of the established approach was proven by the lower limit of quantification of 0.73 ng/mL. The Analytical GREEness calculator results revealed the high level of greenness of the developed method. The PAB's metabolic stability (t1/2 of 18.5 min and a moderate clearance (Clint) of 44.8 mL/min/kg) suggests a high extraction ratio medication that matched the WhichP450 software results. [ABSTRACT FROM AUTHOR]

Zotizalkib (ZTK, TPX‐0131) is a fourth‐generation highly effective inhibitor of wild‐type anaplastic lymphoma kinase (ALK) and ALK‐resistant mutations that can penetrate the central nervous system. It exhibited greater potency compared to all five officially approved ALK inhibitors. The aim of this study was to develop a rapid, accurate, eco‐friendly, and highly sensitive ultra‐high‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS) method for measuring the concentration of ZTK in human liver microsomes (HLMs). The validation aspects of the current UHPLC‐MS/MS methodology in the HLMs were conducted in accordance with the bioanalytical method validation standards specified by the US Food and Drug Administration. ZTK and encorafenib were separated using an Agilent C8 column (Eclipse Plus) and an isocratic mobile phase. The calibration curve for the developed ZTK exhibited a linear relationship within the concentration range of 1–3000 ng/mL. The results from the Analytical Green‐ness Metric Approach program (0.76) suggested that the created method demonstrated a significant degree of environmental sustainability. The in vitro half‐life (t1/2) and intrinsic clearance (Clint) of ZTK were determined to be 15.79 min and 51.35 mL/min/kg, respectively that suggests the ZTK exhibits characteristics similar to those of a medication with a high extraction ratio. These approaches are crucial for the progress of novel pharmaceutical development, especially in improving metabolic stability. [ABSTRACT FROM AUTHOR]

Liquiritin (LQ), a kind of flavonoid isolated from licorice, was proven to have great potential in treating heart failure. Pharmacokinetic evaluation is important for demonstrating clinical efficacy and mechanisms, and the prototype drug and its metabolite profiling are important for drug discovery and development. However, the metabolism of LQ in acute myocardial infarction (AMI) model rats still needs to be studied in depth. An information‐dependent acquisition (IDA)‐ultra‐high‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS) method was applied to profile LQ metabolites in AMI model rat plasma. Protein precipitation and extraction were used for sample preparation. Chromatographic separation was achieved using an XSelect BEH C18 column (2.1 × 150 mm, 2.5 μm) using gradient elution method combining 0.1% formic acid and acetonitrile with a flow rate of 0.3 mL/min. Twelve metabolites were identified in IDA mode, sulfation, glucuronidation, methylation, methyl esterification, glutamine conjugation, and valine conjugation, and their composite reactions were presumed as the primary pathways of LQ metabolism. The variation in the peak areas showed that the time to reach the peak drug concentration of LQ and 12 metabolites was within 5 h. In summary, IDA‐bridged UHPLC‐MS/MS from characteristic fragment ions toward confidence‐enhanced identification could effectively screen and profile metabolites. [ABSTRACT FROM AUTHOR]

The concern about the quality of medicinal herbs is becoming important due to the poor quality of commercial products like cosmetics, functional foods, and natural medicine produced from them. However, there is a lack of modern analytical methods to evaluate the constituents of P. macrophyllus until the moment. This paper reports an analytical method based on UHPLC-DAD and UHPLC-MS/MS MRM methods to evaluate the ethanolic extracts of P. macrophyllus leaves and twigs. 15 main constituents were identified using a UHPLC-DAD-ESI-MS/MS profiling. Subsequently, a reliable analytical method was established and successfully used to quantitate the constituent's content using four marker compounds in leaf and twig extracts of this plant. The result obtained from the current study demonstrated the secondary metabolites and the variety of their derivatives in this plant. The analytical method can help evaluate the quality of P. macrophyllus and develop high-value functional materials. [ABSTRACT FROM AUTHOR]

In this study, a rapid and sensitive ultra‐high performance liquid chromatography‐tandem mass spectrometry method was established for the simultaneous determination of four Vitexin‐4"‐O‐glucoside (VOG), Vitexin‐2"‐O‐rhamnoside (VOR), vitexin (VIT), and hyperoside (HP) in plasma, which are representative flavonoids constituents of hawthorn leaves. The four components were separated by CORTECS UPLC C18 column (100 × 3.0 mm, 1.6 µm), using acetonitrile‐water containing 0.02% formic acid and 2 mmol/L ammonium formate as the mobile phase, the gradient elution flow rate was 0.30 mL/min. The analyte was quantified using an electrospray ionization triple quadrupole mass spectrometer. The analytes and baicalin internal standard were performed at m/z 593.2/413.2 for VOG, m/z 577.2/413.1 for VOR, m/z 431.1/310.9 for VIT, m/z 463.2/300 for HP and m/z 445.1/269 for internal standard. Among the four flavonoids, the correlation coefficient of the standard curve of each component is between 0.9939 and 0.9987. After oral administration of hawthorn leaf extract, VOG and VOR showed similar pharmacokinetic characteristics; VIT was eliminated in the body more slowly than the other three flavonoids and distributed more in the tissues; HP can be quickly absorbed in the blood. The developed analytical method has high sensitivity, precision, and accuracy with no interference from plasma components and has been successfully used in pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

Background: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be. Objective: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains. Methods: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) across ten brain regions. Case–control differences were determined by nonparametric Mann–Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD. Results: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum. Conclusions: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions. Plain Language Summary: Decreases in a molecule called pantothenic acid (also known as vitamin B5) have been observed in several areas of the brain in multiple dementia disease, including Alzheimer's disease, Parkinson's disease dementia, and Huntington's disease. However, it is unknown whether such changes also occur in another dementia disease, dementia with Lewy bodies, which shows many of the same symptoms and molecular changes as these conditions. As such, this study was performed in order to determine if and where changes in pantothenic acid occur throughout the dementia with Lewy bodies brain. Using a methodology called liquid chromatography–mass spectrometry, which is able to measure pantothenic acid levels in a highly precise manner in brain tissues, we found that several regions of the dementia with Lewy bodies brain show decreases in pantothenic acid, including some involved in movement such as the substantia nigra and motor cortex, as well as regions associated with cognition and memory such as the hippocampus—looking most similar to the pattern of changes already seen in Alzheimer's disease. It is possible that these changes contribute to the progression of dementia with Lewy bodies; however, further studies need to be performed to determine at what point these changes happen during the disease and how they may contribute to the development of symptoms. [ABSTRACT FROM AUTHOR]

In this study, UHPLC-HRMS analysis of the defatted methanol extract obtained from Inula salicina L. led to the identification of 58 compounds—hydroxycinnamic and hydroxybenzoic acids and their glycosides, acylquinic and caffeoylhexaric acids, and flavonoids and their glycosides. In addition, a new natural compound, N-(8-methylnepetin)-3-hydroxypiperidin-2-one was isolated and its structure was elucidated by NMR spectroscopy. The presence of a flavoalkaloid in genus Inula is described now for the first time. Chlorogenic acid was the main compound followed by 3,5-, 1,5- and 4,5-dicaffeoylquinic acids. The methanol extract was studied for its antioxidant potential by DPPH, ABTS, and FRAP assays and sun protective properties. In addition, a study was conducted to assess the effectiveness of the tested extract in inhibiting biofilm formation by Gram-positive and Gram-negative strains. Results from crystal violet tests revealed a notable decrease in biofilm mass due to the extract. The anti-biofilm efficacy was confirmed through the observation of the biofilm viability by live/dead staining. The obtained results showed that this plant extract could be used in the development of cosmetic products with antibacterial and sun protection properties. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Guangdong Pharmaceutical University is the property of Journal of Guangdong Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Agricultural Science & Technology (1008-0864) is the property of Journal of Agricultural Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

LC-MS/MS analyses have been reported as challenging for the reliable separation and quantification of cyanogenic glycosides (CNGs), especially (R)-prunasin and sambunigrin isomers found in American elderberry (Sambucus nigra L. subsp. canadensis (L.) Bolli). Hence, a novel multiple reaction monitoring (MRM)-based ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated in the present study for simultaneous separation and quantification of five CNGs, including amygdalin, dhurrin, linamarin, (R)-prunasin, and (S)-prunasin (commonly referred to as sambunigrin). Initially, the role of ammonium formate was investigated as an aqueous mobile-phase additive in developing MRM-based UHPLC-MS/MS. Later, chromatographic conditions for the resolved separation of (R)-prunasin and sambunigrin were identified. Validation studies confirmed that the developed method has good linearity and acceptable precision and accuracy. A noticeable matrix effect (mainly signal enhancement) was observed in leaf samples only. This method was used to detect and quantify CNGs, including (R)-prunasin and sambunigrin, in leaf and fruit samples of American elderberry. Among the studied CNGs, only (R)-prunasin was detected in the leaf samples. Interestingly, (S)-prunasin (sambunigrin) was not detected in the samples analyzed, even though it has been previously reported in elderberry species. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown. Method: In this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared. Result: The modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The Cmax of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier Tmax and greater Cmax and AUC0-t, and the Cmax and AUC0-t of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs. Conclusion: An UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the in vivo exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose. [ABSTRACT FROM AUTHOR]

Much more attention has been paid to the contamination of Alternaria toxins because of food contamination and the threat to human health. In this study, an ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method was developed for the simultaneous detection of the prototypical alternariol, alternariol monomethylether, and the metabolites 4‐oxhydryl alternariol, and alternariol monomethylether 3‐sulfate ammonium salt of Alternaria toxins. The positive samples were used as matrix samples to optimize the different experimental conditions. 0.01% formic acid solution and acetonitrile were used as the mobile phase, and analytes were scanned in negative electron spray ionization under multiple reaction monitoring, and quantitative determination by isotope internal standard method. Application of this method to samples of human plasma and urine showed the detection of the above analytes. The results showed that the recoveries were from 80.40% to 116.4%, intra‐day accuracy was between 0.6% and 8.0%, and inter‐day accuracy was between 1.1% and 12.1%. The limit of detection of the four analytes ranged from 0.02 to 0.6 µg/L in urine, and 0.02 to 0.5 µg/L in plasma, respectively. Thus, the developed method was rapid and accurate for the simultaneous detection of analytes and provided a theoretical basis for the risk assessment of Alternaria toxins for human exposure. [ABSTRACT FROM AUTHOR]

In this study, based on ethnobotanical data recorded in Transylvania, the polyphenolic compounds and the permeability of the aerial part's extract of Tanacetum balsamita were investigated. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was applied for the analysis of the extracts. Parallel artificial membrane permeability assay (PAMPA) for the gastrointestinal tract and the blood–brain barrier was conducted. In the ethanolic and aqueous extracts of the species traditionally used for wound, furuncle, and liver disorders, 92 polyphenols were characterized (e.g., flavonoid, hydroxycinnamic acid, catechin, dihydroxybenzoyl, lignan derivatives, and a monoterpene) including 54 compounds identified for the first time in the plant. In the PAMPA tests, eight components were shown to be capable of passive diffusion across the studied membranes. These include apigenin and seven methoxylated flavonoid derivatives. Based on these results, methoxylated flavonoids might promote the pharmacological potential of T. balsamita to be applied in the enhancement of novel remedies. [ABSTRACT FROM AUTHOR]

Epimedium-Rhizoma drynariae (EP-RD) was a well-known herb commonly used to treat bone diseases in traditional Chinese medicine. Nevertheless, there was incomplete pharmacokinetic behavior, metabolic conversion and chemical characterization of EP-RD in vivo. Therefore, this study aimed to establish metabolic profiles combined with multicomponent pharmacokinetics to reveal the in vivo behavior of EP-RD. Firstly, the diagnostic product ions (DPIs) and neutral losses (NLs) filtering strategy combined with UHPLC-Q-Orbitrap HRMS for the in vitro chemical composition of EP-RD and metabolic profiles of plasma, urine, and feces after oral administration of EP-RD to rats were proposed to comprehensively characterize the 47 chemical compounds and the 97 exogenous in vivo (35 prototypes and 62 metabolites), and possible biotransformation pathways of EP-RD were proposed, which included phase I reactions such as hydrolysis, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, isomerization, and demethylation and phase II reactions such as glucuronidation, acetylation, methylation, and sulfation. Moreover, a UHPLC-MS/MS quantitative approach was established for the pharmacokinetic analysis of seven active components: magnoflorine, epimedin A, epimedin B, epimedin C, icariin, baohuoside II, and icariin II. Results indicated that the established method was reliably used for the quantitative study of plasma active ingredients after oral administration of EP-RD in rats. Compared to oral EP alone, the increase in area under curves and maximum plasma drug concentration (P < 0.05). This study increased the understanding of the material basis and biotransformation profiles of EP-RD in vivo, which was of great significance in exploring the pharmacological effects of EP-RD. [ABSTRACT FROM AUTHOR]

Stanozolol, a synthetic derivative of testosterone, is one of the common doping drugs among athletes and bodybuilders. It is metabolized to a large extent and metabolites are detected in urine for a longer duration than the parent compound. In this study, a novel dummy molecularly imprinted polymer (DMIP) is developed as a sorbent for solid-phase extraction of stanozolol metabolites from spiked human urine samples. The optimized DMIP is composed of stanozolol as the dummy template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker in a ratio of 1:10:80. The extracted analytes were quantitively determined using a newly developed and validated ultrahigh-performance liquid chromatography tandem mass spectrometry method, where the limits of detection and quantitation were 0.91 and 1.81 ng mL−1, respectively, fulfilling the minimum required performance limit decided on by the World Anti-Doping Agency. The mean percentage extraction recoveries for 3'-hydroxystanozolol, 4β-hydroxystanozolol, and 16β-hydroxystanozolol are 97.80% ± 13.80, 83.16% ± 7.50, and 69.98% ± 2.02, respectively. As such, the developed DMISPE can serve as an efficient cost-effective tool for doping and regulatory agencies for simultaneous clean-up of the stanozolol metabolites prior to their quantification. [ABSTRACT FROM AUTHOR]

Hedysari Radix is a commonly used traditional Chinese medicine that improves immunity; formononetin, ononin, calycosin, medicarpin, and vanillic acid play an important role in achieving this effect. Herein, a precise and sensitive ultra‐high‐performance‐tandem mass spectrometry method was developed and validated for the determination of five bioactive components that were extracted from plasma using a protein precipitation method. A Waters CORTES C18 (4.6 × 50 mm, 2.7 µm) and a mobile phase composed of methanol and water (containing 0.2% formic acid) were used for the separation. The method was linear within the concentration range of 19.53–625.00 ng/mL for formononetin; 0.01–3.13 ng/mL for ononin; 0.01–3.13 ng/mL for calycosin; 0.16–5.00 ng/mL for medicarpin; and 19.53–625.00 ng/mL for vanillic acid. This method has a lower limit of quantification, is simple, and has a short analysis time and a high degree of separation. The intra‐day precisions and inter‐day precisions of quality control samples were traced to be below 8.58% and 12.64%, respectively. Fidelity intervened from −8.61% to 10%. Finally, the developed method was used to determine the concentrations of the five bioactive components in rat plasma after the administration of rubbing‐ and non‐rubbing processed Hedysari Radix. [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]

Chamazulene (CA) is an intensely blue molecule with a wealth of biological properties. In cosmetics, chamazulene is exploited as a natural coloring and soothing agent. CA is unstable and tends to spontaneously degrade, accelerated by light. We studied the photodegradation of CA upon controlled exposure to UVB-UVA irradiation by multiple techniques, including GC-MS, UHPLC-PDA-ESI-MS/MS and by direct infusion in ESI-MSn, which were matched to in silico mass spectral simulations to identify degradation products. Seven byproducts formed upon UVA exposure for 3 h at 70 mW/cm2 (blue-to-green color change) were identified, including CA dimers and CA benzenoid, which were not found on extended 6 h irradiation (green-to-yellow fading). Photostability tests with reduced irradiance conducted in various solvents in the presence/absence of air indicated highest degradation in acetonitrile in the presence of oxygen, suggesting a photo-oxidative mechanism. Testing in the presence of antioxidants (tocopherol, ascorbyl palmitate, hydroxytyrosol, bakuchiol, γ-terpinene, TEMPO and their combinations) indicated the highest protection by tocopherol and TEMPO. Sunscreens ethylhexyl methoxycinnamate and particularly Tinosorb® S (but not octocrylene) showed good CA photoprotection. Thermal stability tests indicated no degradation of CA in acetonitrile at 50 °C in the dark for 50 days; however, accelerated degradation occurred in the presence of ascorbyl palmitate. [ABSTRACT FROM AUTHOR]

Topotecan (TPT) is used in the treatment of retinoblastoma, the most common malignant intraocular tumor in children. TPT undergoes pH‐dependent hydrolysis of the lactone ring to the ring‐opened carboxylate form, with the lactone form showing antitumor activity. A selective, and highly sensitive ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method was developed for the determination of both forms of TPT in one mobile phase composition in plasma and vitreous humor matrices. The method showed an excellent linear range of 0.375–120 ng/mL for the lactone. For the carboxylate, the linear range was from 0.75 to 120 ng/mL. The matrix effect and the recovery for the lactone ranged from 98.5% to 106.0% in both matrices, for the carboxylate form, it ranged from 94.9% to 101.2%. The dynamics of the transition between TPT lactone and TPT carboxylate were evaluated at different pH environments. The stability of TPT forms was assessed in plasma and vitreous humor at 8 and 37°C and a very fast conversion of lactone to carboxylate form occurred at 37°C in both matrices. The method developed facilitates the investigation of TPT pharmacodynamics and the release kinetics in the development of the innovative local drug delivery systems. [ABSTRACT FROM AUTHOR]

Spontaneous bacterial peritonitis is a frequent severe complication in cirrhotic patients with ascites. Carbapenem antibiotics are currently the treatment of choice for patients with hospital-acquired or healthcare-related infections. However, there is limited evidence available on the efficacy of ertapenem in cirrhotic patients with spontaneous bacterial peritonitis. As a result, the pharmacokynetics and pharmacodynamics of this antibiotic are still unknown. The objective of this study was to develop and validate measurement procedures based on liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine ertapenem concentrations in plasma and ascitic fluid. Samples were pretreated by acetronile protein-precipitation. Chromatographic separation is performed on a C18 reversed-phase Acquity®-UPLC®-BEHTM column (2.1 × 100 mm id, 1.7 µm) using a non-linear gradient of water/acetonitrile containing 0.1 % of formic acid at a flow rate of 0.4 mL/min. Ertapenem and its internal standard (ertapenem-D4) are detected by tandem mass spectrometry using positive electrospray ionization and multiple reaction monitoring, and using 476.2 → 346.0/432.2 as mass transition for ertapenem and 480.2 → 350.0 for its internal standard. No significant interferences or carry-over contamination were observed. Imprecisions, absolute relative bias, matrix effects and normalized recoveries were ≤14.5 %, ≤9.3 % (92.8–104.5) % and (98.8–105.8) %, respectively. Chromatographic measurement procedures were linear from (0.50–100) mg/L. The measurement procedures based on UHPLC-MS/MS developed and validated in this study could be useful in pharmacokynetic and pharmacodynamic studies in subjects with liver cirrhosis who develop spontaneous bacterial peritonitis treated with ertapenem. [ABSTRACT FROM AUTHOR]

Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL−1). [ABSTRACT FROM AUTHOR]