Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD₀₁, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.     

HPLC-MS测定白酒中氨基甲酸酯类农药残留

建立了一种同时对白酒中10种氨基甲酸酯类农药残留的HPLC-MS测定方法。色谱条件:色谱柱Phenomenex-LunaCN100A(250mm×4.6mm×5μm),流动相乙腈-水(在40min内乙腈由20%变为80%),流速1.00mL/min,检测波长195nm,柱温25℃,进样量20μL。质谱条件:电喷雾离子源(ESI+源),扫描范围(m/z)为50～350,干燥气温度350℃,干燥气流速8.0mL/min,雾化气压力275.86kPa。样品制备:白酒样品用固相萃取处理后,氮吹浓缩,乙腈定容至2mL。结果表明,10种氨基甲酸酯类农药残留在0.05～3μg范围积线性关系良好,相关系数R2>0.99。平均回收率在72.6%和97.6%,RSD在2.6%～5.9%之间。结论:方法灵敏度高、操作简便、结果准确,可用于酒样中痕量农药残留的含量测定。     

Dietary exposure of Hong Kong adults to pesticide residues: results of the first Hong Kong total diet study

The use of pesticides and other chemicals has become a common practice in modern agriculture to enhance and stabilise crop yield, protect the nutritional integrity of food, facilitate food storage to assure year-round supplies, and provide attractive and appealing food products. With the adoption of strict good agricultural practice (GAP), only minimal amounts of pesticide residues should remain on the crops or in connected foods of animal origin up the food chain. To assess their associated health risk to local people, the dietary exposure of Hong Kong adults to residues of four groups of pesticides or their metabolites – organophosphorus pesticides (OPPs), carbamates, pyrethrins and pyrethroids, and dithiocarbamate (DTC) metabolites – is estimated in the first Hong Kong Total Diet Study (TDS). A total of 150 commonly consumed food items were collected and prepared “as consumed”. A total of 600 composite food samples were analysed for 85 pesticides or their metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS). These pesticides were primarily found at low levels (highest mean = 350 μg kg^?1) in food samples of plant origin such as vegetables and fruits. Dietary exposures to pesticide residues were estimated based on the analytical results and the food consumption data of the local residents. The estimated dietary exposures of Hong Kong adults to all individual pesticides were well below their respective acceptable daily intakes (ADIs). The percentage contributions of the estimated mean and 95th percentile dietary exposures to the ADIs of individual pesticides were <6% and <24% for the OPPs, <1% for the carbamates and pyrethrins and pyrethroids, and <1% and <4% for the DTC metabolites, respectively. The findings indicate that dietary exposures to all the pesticide residues analysed in this study were unlikely to pose unacceptable health risks to the Hong Kong population.     

Double Repositioning: Veterinary Antiparasitic to Human Anticancer

Drug repositioning, the approach of discovering different uses for existing drugs, has gained enormous popularity in recent years in the anticancer drug discovery field due to the increasing demand for anticancer drugs. Additionally, the repurposing of veterinary antiparasitic drugs for the treatment of cancer is gaining traction, as supported by existing literature. A prominent example is the proposal to implement the use of veterinary antiparasitics such as benzimidazole carbamates and halogenated salicylanilides as novel anticancer drugs. These agents have revealed pronounced anti-tumor activities and gained special attention for “double repositioning”, as they are repurposed for different species and diseases simultaneously, acting via different mechanisms depending on their target. As anticancer agents, these compounds employ several mechanisms, including the inhibition of oncogenic signal transduction pathways of mitochondrial respiration and the inhibition of cellular stress responses. In this review, we summarize and provide valuable information about the experimental, preclinical, and clinical trials of veterinary antiparasitic drugs available for the treatment of various cancers in humans. This review suggests the possibility of new treatment options that could improve the quality of life and outcomes for cancer patients in comparison to the currently used treatments.     

超高效液相色谱-串联质谱法测定蔬菜中4种氨基甲酸酯类农药残留量

目的建立超高效液相色谱-串联质谱法测定蔬菜中4种氨基甲酸酯类农药残留量。方法蔬菜样品经切碎,乙腈提取,分别用固相萃取柱及QuEChERS净化后,以乙腈-0.1%甲酸水溶液为流动相梯度洗脱,经CAPCELL PAK C₁₈色谱柱分离,采用多反应监测正离子模式(multireaction monitoring in positive ion mode,MRM)对异丙威、仲丁威、残杀威、克百威4种氨基甲酸酯类农药进行定性和定量分析。结果 4种氨基甲酸酯类农药在给定标准溶液浓度范围内峰面积与浓度呈良好线性关系,相关系数均大于0.999,检出限为0.001~0.005 mg/kg,平均回收率为70%~130%,相对标准偏差均小于20%。结论本方法灵敏度高、检出限低、回收率好、操作可行,可实现蔬菜中多种氨基甲酸酯类农药的同时测定。     

New strategies for the Hofmann reaction

Some new strategies, such as the use of hydrotropes, surfactants, co-solvent, etc., were applied to the Hofmann reaction of fatty amides to obtain isocyanates, amines and carbamates. Additionally, some industrially important aromatic amines were synthesised.     

CO2 Capture by Liquid Solvents and their Regeneration by Thermal Decomposition of the Solid Carbonated Derivatives

The chemical capture of CO₂ by either aqueous Na₂CO₃ and K₂CO₃ or nonaqueous solutions of the amines 2‐amino‐2‐methyl‐1‐propanol (AMP) or piperazine (PZ) is described. The captured CO₂ is stored as solid NaHCO₃, KHCO₃, and AMP or PZ carbamates. Solid NaHCO₃ and KHCO₃ are decomposed at 200 °C and 250 °C, respectively, to regenerate the carbonates for their reuse. In the experiments with AMP or PZ, the solid carbamates are decomposed at 80 °C–110 °C to regenerate the free amines. The absence of water in the desorption‐regeneration step is intriguing and could have the potential of reducing one of the major disadvantages of aqueous absorbents, namely the energy cost of the regeneration step and amine degradation, yet preserving the efficiency of the absorption in the liquid phase.     

Residue analysis of 500 high priority pesticides: Better by GC–MS or LC–MS/MS?

This overview evaluates the capabilities of mass spectrometry (MS) in combination with gas chromatography (GC) and liquid chromatography (LC) for the determination of a multitude of pesticides. The selection of pesticides for this assessment is based on the status of production, the existence of regulations on maximum residue levels in food, and the frequency of residue detection. GC-MS with electron impact (EI) ionization and the combination of LC with tandem mass spectrometers (LC-MS/MS) using electrospray ionization (ESI) are identified as techniques most often applied in multi-residue methods for pesticides at present. Therefore, applicability and sensitivity obtained with GC-EI-MS and LC-ESI-MS/MS is individually compared for each of the selected pesticides. Only for one substance class only, the organochlorine pesticides, GC-MS achieves better performance. For all other classes of pesticides, the assessment shows a wider scope and better sensitivity if detection is based on LC-MS.     

Synthesis of Aryl Carbamates via Copper‐Catalyzed Coupling of Aryl Halides with Potassium Cyanate

Coupling of aryl halides with potassium cyanate takes place at 100–110 °C in alcohols under the catalysis of CuI (cuprous iodide) and 2‐(2,6‐dimethylphenylamino)‐2‐oxoacetic acid, affording the corresponding aryl carbamates with great diversity.     

酶抑制—比色法在农药残留快速检测中的研究进展

概述酶抑制- 比色法在农药残留快速检测中的检测原理、对不同种酶源的选择与保存、酶抑制法检测条件及改进方法等研究进展,并指出酶抑制- 比色法在使用中存在的问题和未来的发展趋势。