A fast method for the determination of personal care product chemicals in human urine using dispersive liquid-liquid extraction and ultra high-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: Personal care product chemicals (PCPCs) are the chemicals used in personal care products. Many of them are endocrine disruptors and have potential adverse effects on humans. The concentrations of PCPCs in urine are the main biomarker for assessing human exposure. METHODS: A method was developed for the simultaneous determination of 14 PCPCs in human urine using dispersive liquid-liquid extraction combined with ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Compared with liquid-liquid extraction, this method had the advantages of time efficiency, sensitivity, and limited organic solvent consumption. It produced good linearity (0.9965-0.9996), limits of detection (2.82-36.36 pg mL-1 ), limits of quantitation (9.39-121.08 pg mL-1 ), matrix effect (-0.90%-2.55%), intra-day precision (relative standard deviations [RSDs] <15%), and inter-day precision (RSDs <19.9%). The method had satisfactory relative recovery at three concentration levels. CONCLUSIONS: A rapid method was developed for the simultaneous quantification of 14 PCPCs in human urine. The practicability of the method was verified with 21 urine from university students. It is expected that this method will provide a powerful reference for the assessment of exposure to PCPCs in large populations.

Traditional and Novel Organophosphate Esters in Plastic Greenhouse: Occurrence, Multimedia Migration, and Exposure Risk via Vegetable Consumption.

The migration and risk of organophosphate esters (OPEs) in agricultural air-soil-plant multimedia systems due to plastic film application remain unclear. This study investigates the multimedia distribution of traditional OPEs (TOPEs), novel OPEs (NOPEs), and their transformation products (POPEs) in plastic and solar greenhouses. The total concentration of OPE-associated contaminants in air and airborne particles ranged from 594 to 1560 pg/m3 and 443 to 15600 ng/g, respectively. Significant correlations between air OPE concentrations and those in polyolefin film (P < 0.01) indicate plastic film as the primary source. Contaminants were also found in soils (96.8-9630 ng/g) and vegetables (197-7540 ng/g). The primary migration pathway for NOPEs was particle dry deposition onto the soil and leaf, followed by plant accumulation. Leaf absorption was the main uptake pathway for TOPEs and POPEs, influenced by vegetable specific leaf surface area. Moreover, total exposure to OPE-associated contaminants via vegetable intake was assessed at 2250 ng/kg bw/day for adults and 2900 ng/kg bw/day for children, with an acceptable hazard index. However, a high ecological risk was identified for NOPE compounds (median risk quotient, 975). This study provides the first evidence of the multimedia distribution and potential threat posed by OPE-associated contaminants in agricultural greenhouses.

Adverse events related to neuromuscular blocking agents: a disproportionality analysis of the FDA adverse event reporting system.

Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in "cardiac disorders," "immune system disorders," "respiratory, thoracic and mediastinal disorders" and "vascular disorders." At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study.

HMG-CoA reductase inhibitor from the endophytic fungus Colletotrichum Capsici.

Two new fungal polyketides with unusual skeleton, collecapsins A and B (1-2), along with two known macrolactins A and B (3-4), were isolated from the rice cultures of an endophytic fungus Colletotrichum capsici obtained from the fresh Siegesbeckia pubescens Makino. Their structures were established by a combination of NMR, HRESIMS, and IR analysis. The absolute configurations of 1 and 2 were determined on the detailed analysis of the modified Mosher's derivatives' spectra and its key NOEs correlations. In this case, the absolute configurations of all chiral centres of 1 were determined for the first time, showed that 1 is a C-6/C-8 epimer of colletruncoic acid methyl ester. Compounds 1-2 demonstrated promising lipid lowing activity via the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase with IC50 values of 8.72 and 15.28 µM. Compounds 3-4 exhibited antibacterial activity with MIC values ranging from 0.25-25.8 µM.