Unintentional ingestion of pharmacologically-active substances through foods and dietary supplements presents growing challenges for food safety and anti-doping regulation. We developed a high-throughput LC-MS/MS platform to simultaneously screen 331 compounds and quantify 214 analytes, with matrix-matched validation in pork, oat, and beverage. The method showed applicability across ten food types and was applied to seventy-eight commercial products, revealing frequent detection of bioactives such as octopamine, coclaurine, and olodaterol. Simulations of dietary exposure and urinary excretion demonstrated that some of these substances exceed World Anti-Doping Agency reporting thresholds under realistic consumption scenarios, risking adverse analytical findings even without intentional use. This study presents an integrated framework linking analytical detection with exposure assessment, enabling proactive identification of regulatory-relevant substances across complex food matrices. The approach provides a practical tool for monitoring foodborne chemical exposure and supports risk management for both the general population and athletes subject to strict doping control standards.

Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain. Using a mouse model with cell-specific hyperactivation of NLRP3, we identify microglial NLRP3 activation as essential for peripheral inflammation-induced BBB disruption. Conversely, NLRP3 and microglial gasdermin D (GSDMD) deficiency markedly attenuates lipopolysaccharide-induced BBB breakdown. Notably, IL-1β is not required for NLRP3-GSDMD-mediated BBB disruption. Instead, microglial NLRP3-GSDMD axis upregulates CXCL chemokines and matrix metalloproteinases around BBB via producing GDF-15, promoting the recruitment of CXCR2-containing neutrophils. Inhibition of neutrophil infiltration and matrix metalloproteinase activity significantly reduces NLRP3-mediated BBB impairment. Collectively, these findings reveal the important role of NLRP3-driven chemokine production in BBB disintegration, suggesting potential therapeutic targets to mitigate neuroinflammation. The biological mechanisms regulating blood-brain barrier integrity remain unclear. Here, the authors identify microglial NLRP3-gasdermin D signaling as a driver of blood-brain barrier disruption during peripheral inflammation in mice, mediated by CXCL-dependent neutrophil recruitment.

The release of hydrogen cyanide (HCN) after food ingestion can pose a serious health risk to consumers. This study aimed to simultaneously quantify four cyanogenic glycosides (lotaustralin, prunasin, taxiphyllin, and dhurrin) using liquid chromatography-tandem mass spectrometry. The analysis scope extended beyond agricultural products to various consumer foods to estimate dietary exposure to cyanogenic glycosides and assess its risk levels. The major exposure sources are cassava chips (lotaustralin), apples (seeds) (prunasin and dhurrin), and Prunus mume axis (taxiphyllin). In addition to quantifying specific cyanogenic glycosides, this study proposed the development of a preliminary risk assessment framework based on the dietary exposure assessment and the calculation of theoretical levels of HCN derived from cyanogenic glycoside concentrations. In the absence of established guidelines for the permissible intake of foods containing cyanogenic glycosides, this study provides initial guidance for assessing the risks associated with a range of commonly consumed foods.

As beta-carboline (beta C) alkaloids, posing potential health risks, are present in a wide variety of foods, determining the exposure degrees of food to these alkaloids from dietary activity is key to ensuring food safety. Here, we developed a rapid and sensitive simultaneous analytical method for six beta C alkaloids in food. We optimized the buffered QuEChERS method, which includes a clean-up process through dispersive solid phase extraction, to extract the target compounds from food matrices; then, these compounds were detected via liquid chromatography-tandem mass spectrometry. We established calibration ranges for each target compound and matrix within the range of 0.05-250 mu g/kg, and verified linearity (R2 >= 0.99) and limit of quantitation (<= 1.63 mu g/kg). Furthermore, we validated trueness (85.8%-118.8%) and precision (<= 18.7%) at three levels within the calibration range, including the lowest and highest concentrations. Finally, we employed the developed method to determine the beta C alkaloid contents in 304 samples of 41 food items and dietary exposure of six beta C alkaloids resulting from daily intake. Although beta C alkaloids were detected in 86.2% of the samples, exposure level to the 41 food items was insufficient to cause toxicity.

Ricinine, a toxic compound found in castor plants (Ricinus communis), causes abdominal pain, nausea, and vomiting. Castor leaves and castor oil-based dietary supplements are commonly consumed, but their ricinine content has not been evaluated for safety. This study aimed to determine the ricinine concentration in these products and to evaluate the ricinine exposure level from their consumption. The developed method combines the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) technique and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A matrix-matched calibration method for castor leaves is then proposed, which demonstrates high linearity over a wide concentration range (50-1000 & mu;g/kg; r2 > 0.995). The intraday and interday accuracies ranged from 93.6% to 113.7%; the precisions were within 10%. The limits of detection and quantitation were & LE; 8.9 & mu;g/kg and & LE; 26.9 & mu;g/kg, respectively, and this validated method was successfully applied to commercial castor plant-based products. Ricinine exposure from the consumption of these foods was estimated to be 0.0001-0.2792 & mu;g/kg body weight/day. This study assesses the safety of castor plant-based food products and could help prevent potential health risks associated with ricinine consumption.

Ptaquiloside, a naturally occurring cancer-causing substance in bracken fern, has been detected in the meat and milk of cows fed a diet containing bracken fern. A rapid and sensitive method for the quantitative analysis of ptaquiloside in bracken fern, meat, and dairy products was developed using the QuEChERS method and liquid chromatography–tandem mass spectrometry. The method was validated according to the Association of Official Analytical Chemists guidelines and met the criteria. A single matrix-matched calibration method with bracken fern has been proposed, which is a novel strategy that uses one calibration for multiple matrices. The calibration curve ranged from 0.1 to 50 µg/kg and showed good linearity (r2 > 0.99). The limits of detection and quantification were 0.03 and 0.09 µg/kg, respectively. The intraday and interday accuracies were 83.5–98.5%, and the precision was <9.0%. This method was used for the monitoring and exposure assessment of ptaquiloside in all routes of exposure. A total of 0.1 µg/kg of ptaquiloside was detected in free-range beef, and the daily dietary exposure of South Koreans to ptaquiloside was estimated at up to 3.0 × 10−5 µg/kg b.w./day. The significance of this study is to evaluate commercially available products in which ptaquiloside may be present, to monitor consumer safety.

Brain doping is a novel form of doping that involves stimulating specific brain regions to enhance sports performance. However, to the best of our knowledge, there is currently no established provision or detection method for it. As brain stimulation ultimately induces alterations in neurochemical concentrations, this study aimed to develop a diagnostic strategy for brain doping. We successfully developed and validated a sensitive simultaneous analysis method for 23 neurochemicals present in urine. Simple derivatization was employed to overcome ionization efficiency, enabling the effective detection of all the target compounds within 5 min. Additionally, we developed an animal model system using rats to replicate brain-doping scenarios and establish a diagnostic strategy. Behavior tests confirmed improved sports performance in the brain stimulation group. By examining changes in the distribution patterns of the target substances in urine samples, we observed that neurochemicals could be used as potential biomarkers for brain-doping diagnosis. The developed method allows the effective simultaneous analysis of multiple neurochemicals in biological samples and is expected to have various applications, including doping control. Thus, changes in the distribution pattern of neurochemicals could serve as a basis for brain-doping diagnosis.

Lycorine, a prominent alkaloid found in the Amaryllidaceae plant family, is known for its therapeutic properties and potential applications. However, excessive lycorine consumption can cause food poisoning and other detrimental health effects. This study focuses on the quantitative measurement of lycorine levels in commercially available foods and an evaluation of dietary exposure. With regard to this, considerable research has not been conducted to date. For the analysis of lycorine, a Quick, Easy, Cheap, Effective, Rugged, Safe (QuEChERS) technique, and a liquid chromatography-tandem mass spectrometry method were developed, validated, and applied to 56 commercial food samples and 5 Amaryllidaceae plants. The calculated dietary exposure ranged from 0.0 to 3.77 x 10-4 and 0.39-4.72 mu g/kg bw/day in lycorine detected foods and Amaryllidaceae plants, respectively (Allium cepa, Allium hookeri, Allium monanthum, Perilla leaves, and Amaryllidaceae plants). Foods in the Amaryllidaceae family were more likely to contain lycorine, with onion identified as a primary food source contributing to lycorine exposure. These findings help to accurately determine the lycorine content in foods, identify potential benefits and risks associated with the consumption of lycorine-containing foods, and may support the need for further research to establish appropriate guidelines for the consumption of these foods.

Ricinine, an alkaloid plant toxin present in castor leaf (Ricinus communis), causes abdominal pain, nausea and vomiting. In South Korea, castor leaves are consumed as foods and castor leaves or oil-based dietary supplements are commercially available. This study validates a rapid and reliable method for quantifying ricinine levels in natural products and dietary supplements. The method combines the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) technique and liquid chromatography–tandem mass spectrometry (LC/MS). A matrix-matched calibration method for castor leaves is then proposed, which demonstrates high linearity over a wide concentration range (50–1000 µg/kg; r2 > 0.995). The intra- and inter-day precisions were within 10% and the accuracies ranged from 93.6% to 113.7%. The limits of detection and quantification were ≤8.9 µg/kg and ≤26.9 µg/kg, respectively. The fully validated QuEChERS–LC/MS-based method successfully applied for monitoring and exposure assessment of ricinine from commercial castor-based products.