Veterinary Drugs

兽药
  • 文章类型: Journal Article
    畜禽肉类消费在我国居民膳食结构中占有重要地位。然而,湖南省畜禽肉及其副产品中兽药残留和重金属污染的程度尚未得到广泛研究。这项调查旨在通过评估湖南省76种兽药残留来填补这一空白。此外,还评估了猪肉和猪肝中的重金属。获得的结果表明,兽药残留仍然存在于畜禽肉类中,以及他们的副产品,在湖南省内。然而,重金属污染仍在食品安全范围内。这些结果强调了建立更完善的评估人类暴露标准的重要性,考虑到消费模式等因素,产品品种和感兴趣的化合物。
    Livestock and poultry meat consumption play an important role in the dietary structure of Chinese residents. However, the extent of residues of veterinary drugs and heavy metal contamination in livestock and poultry meat and their by-products within Hunan province is not extensively studied. This survey aimed to fill this gap by assessing the presence of 76 veterinary drug residues in Hunan province. Additionally, heavy metals in pork and pig liver were also assessed. The obtained findings suggest that residues of veterinary drugs are still present in livestock and poultry meat, as well as their by-products, within Hunan province. However, the contamination of heavy metals remained within the food safety limits. These results underscore the significance of establishing more refined criteria for assessing human exposure, taking into account factors such as consumption patterns, product varieties and chemical compounds of interest.
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  • 文章类型: English Abstract
    牛奶是一种重要的消费品,具有很高的营养价值。由于滥用兽药而导致牛奶中兽药残留的存在可能会影响消费者的健康。在痕量化合物的质谱分析中,色谱共洗脱组分容易干扰获得的质谱信号,影响定性和定量分析的准确性。基质纯化是减少基质效应的一种有前途的方法。壳聚糖是一种天然生物聚合物,具有许多活性官能团,如氨基,乙酰基,和羟基;这些基团可以通过疏水和静电相互作用吸附脂质。壳聚糖还具有生产成本低的优点,化学性质稳定,和方便的修改。新型基于壳聚糖的材料是用于脂质纯化的有希望的候选物。在这项研究中,用三甲氧基十八烷基硅烷(C18-CSM)改性壳聚糖膜。C18-CSM通过一步水解制备,并用作分散固相萃取(DSPE)吸附剂,以在牛奶预处理过程中纯化基质。我们将C18-CSM与超高效液相色谱-四极杆/静电场轨道阱质谱(UHPLC-Q/ExactiveOrbitrapMS)相结合,建立了一种有效的氧氟沙星提取和测定方法,恩诺沙星,环丙沙星,地西泮,还有牛奶中的甲硝唑.C18-CSM使用扫描电子显微镜进行表征,傅里叶变换红外光谱,和水接触角测试。结果表明,该材料具有粗糙的表面和均匀致密的横截面。C18-CSM的水接触角为104°,表明其良好的疏水性。预处理条件(萃取溶剂,NaCl用量,提取频率,详细研究了影响五种兽药回收率的C18-CSM)剂量。建立了最佳工艺条件:5%甲酸,乙腈,1克NaCl,提取1次,20毫克C18-CSM。在HypersilGOLDVANQUISH色谱柱上进行分离(100mm×2.1mm,1.9μm)。流动相为0.1%甲酸水溶液和0.1%甲酸的乙腈溶液,并且以0.3mL/min的速率流动。进样体积为1μL,柱温保持在25℃。以正电喷雾电离模式进行质谱分析。为了验证净化材料的必要性,采用基质匹配标准曲线法研究基质效应.C18-CSM的使用将五种必需药物的基质效应从-22%-8.8%的范围降低到-13%-3.6%的范围,表明C18-CSM是一种高效的DSPE材料。在最优条件下,所开发的方法在0.5-100μg/L范围内显示出良好的线性,相关系数(r2)≥0.9970。检测限(LODs)和定量限(LOQs)分别为0.2μg/L和0.5μg/L,分别。为了评估该方法的准确性和精密度,我们准备了三个加标水平的牛奶样品(低,中等,和高)。五种兽药的回收率从79.5%到115%不等,日内和日间相对标准偏差分别为7.0%-13%(n=6)和1.3%-11%(n=3),分别。这项研究提供了一个简单的,准确,方法可靠,快速,同时测定牛奶中五种兽药的残留量。
    Milk is an important consumer product with high nutritional value. The presence of veterinary drug residues in milk owing to the indiscriminate use of veterinary drugs may affect consumer health. In the mass spectrometric analysis of trace compounds, chromatographic co-eluting components easily interfere with the mass spectral signals obtained, affecting the accuracy of qualitative and quantitative analyses. Matrix purification is a promising method to reduce the matrix effect. Chitosan is a natural biopolymer with numerous active functional groups such as amino, acetyl, and hydroxyl groups; these groups can adsorb lipids through hydrophobic and electrostatic interactions. Chitosan also has the advantages of low production cost, stable chemical properties, and convenient modification. Novel chitosan-based materials are promising candidates for lipid purification. In this study, a chitosan membrane was modified with trimethoxyoctadecylsilane (C18-CSM). C18-CSM was prepared through one-step hydrolysis and used as a dispersive solid phase extraction (DSPE) adsorbent to purify the matrix during milk pretreatment. We combined C18-CSM with ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry (UHPLC-Q/Exactive Orbitrap MS) to develop an effective method for the extraction and determination of ofloxacin, enrofloxacin, ciprofloxacin, diazepam, and metronidazole in milk. C18-CSM was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle testing. The results indicated that the material has a rough surface and uniformly dense cross-section. The water contact angle of C18-CSM was 104°, indicating its good hydrophobicity. The pretreatment conditions (extraction solvent, dosage of NaCl, extraction frequency, and dosage of C18-CSM) that influenced the recoveries of the five veterinary drugs were investigated in detail. The optimal conditions were established as follows: 5% formic acid in acetonitrile, 1 g NaCl, extraction 1 time, 20 mg C18-CSM. Separation was performed on a Hypersil GOLD VANQUISH column (100 mm×2.1 mm, 1.9 μm). The mobile phase consisted of 0.1% formic acid aqueous solution and 0.1% formic acid in acetonitrile, and was flowed at a rate of 0.3 mL/min. The sample injection volume was 1 μL, and the column temperature was maintained at 25 ℃. Mass spectrometric analysis was performed in positive electrospray ionization mode. To verify the necessity of the purification material, the matrix effect was investigated using the matrix-matched standard curve method. The use of C18-CSM reduced the matrix effects of the five necessity drugs from the range of -22%-8.8% to the range of -13%-3.6%, indicating that C18-CSM is a highly efficient DSPE material. Under optimal conditions, the developed method showed good linearities within the range of 0.5-100 μg/L, with correlation coefficients (r2)≥0.9970. The limits of detection(LODs) and quantification (LOQs) were 0.2 μg/L and 0.5 μg/L, respectively. To assess the accuracy and precision of the method, we prepared milk samples with three spiked levels (low, medium, and high). The recoveries of the five veterinary drugs were ranged from 79.5% to 115%, and the intra-day and inter-day relative standard deviations were 7.0%-13% (n=6) and 1.3%-11% (n=3), respectively. This study provides a simple, accurate, and reliable method for the rapid and simultaneous determination of the five veterinary drug residues in milk.
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  • 文章类型: Journal Article
    牛奶,作为一种广泛食用的营养丰富的食物,对骨骼健康至关重要,增长,和整体营养。用于控制疾病和提高产奶量的兽药的持续应用对人类健康和环境生态系统产生了重大影响。由于需求量大,新鲜消费,牛奶的复杂成分,以及药物残留的潜在不利影响,先进的绿色分析方法是必要的。其中,基于功能材料的分析方法引起了广泛的关注。磁性分子印迹聚合物(MMIP),作为一种典型的功能材料,具有优异的绿色化特性和效力,它们很容易集成到各种检测技术中,它们为牛奶中的兽药等分析物提供了绿色方法。尽管它们的应用越来越多,潜力很大,MMIP在乳制品基质中的使用仍未充分开发,尤其是生态可持续性。这项工作回顾了MMIP合成的最新进展,以及作为牛奶中兽药提取和色谱分析的有效吸附剂的应用。评估了实际牛奶样品中MMIP的独特性和有效性,解决了当前的限制,并提出了绿色化机会。MMIP在彻底改变兽药检测的绿色分析程序方面显示出希望,与现代食品生产系统的环境目标保持一致。
    Milk, as a widely consumed nutrient-rich food, is crucial for bone health, growth, and overall nutrition. The persistent application of veterinary drugs for controlling diseases and heightening milk yield has imparted substantial repercussions on human health and environmental ecosystems. Due to the high demand, fresh consumption, complex composition of milk, and the potential adverse impacts of drug residues, advanced greener analytical methods are necessitated. Among them, functional materials-based analytical methods attract wide concerns. The magnetic molecularly imprinted polymers (MMIPs), as a kind of typical functional material, possess excellent greenification characteristics and potencies, and they are easily integrated into various detection technologies, which have offered green approaches toward analytes such as veterinary drugs in milk. Despite their increasing applications and great potential, MMIPs\' use in dairy matrices remains underexplored, especially regarding ecological sustainability. This work reviews recent advances in MMIPs\' synthesis and application as efficient sorbents for veterinary drug extraction in milk followed by chromatographic analysis. The uniqueness and effectiveness of MMIPs in real milk samples are evaluated, current limitations are addressed, and greenification opportunities are proposed. MMIPs show promise in revolutionizing green analytical procedures for veterinary drug detection, aligning with the environmental goals of modern food production systems.
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  • 文章类型: Journal Article
    目的:报告推测的兽用驱虫药(VADs)诱导的视网膜毒性的光学相干断层扫描结果,这可能有助于了解潜在的致病机制。
    方法:这是一项回顾性观察性病例系列分析,分析了意外或有意服用兽用驱虫药后出现视力异常的患者。所有病例均接受了彻底的眼科检查。此外,医疗记录,以及初始和后续光学相干断层扫描图像,被彻底仔细检查。
    结果:确定了4名患者(3名男性;平均[范围]年龄,36.5[22-52]年)。每位患者过量服用以下一种或两种VAD:closantel,三苯多唑,吡喹酮,pyrantelpamoate,还有Niclofolan.最具特征的光学相干断层扫描发现是漫反射,颗粒状,整个外视网膜的过度反射病变,最初在两种情况下在椭球区中被识别出来。在后续行动中,光学相干断层扫描显示两名患者的高反射病变消退和外部视网膜元素广泛丢失。此外,中央凹下视网膜外层可能部分保留。
    结论:某些兽用驱虫药如果用药过量,可能对人视网膜有害,导致视觉障碍。光学相干断层扫描显示富含线粒体的椭圆体区,在该处首次出现外部视网膜损伤,暗示这些药物可能通过抑制线粒体能量代谢来伤害视网膜,就像他们消灭寄生虫一样。
    OBJECTIVE: To report optical coherence tomography findings of presumed veterinary anthelmintic drugs (VADs)-induced retinal toxicity that may aid in understanding potential pathogenic mechanisms.
    METHODS: This is a retrospective observational case series analysis of patients with vision abnormalities following the accidental or intentional consumption of veterinary anthelmintic drugs. All cases underwent a thorough ophthalmological examination. Moreover, medical records, as well as the initial and follow-up optical coherence tomography images, were thoroughly scrutinized.
    RESULTS: Four patients were identified (3 men; mean [range] age, 36.5 [22-52] years). Each patient overdosed on one or two of the following VADs: closantel, triclabendazole, praziquantel, pyrantel pamoate, and niclofolan. The most characteristic optical coherence tomography finding was diffuse, granular, hyperreflective lesions throughout the outer retina, which were initially identified in the ellipsoid zone in two cases. At follow-up, optical coherence tomography exhibited regression of hyperreflective lesions and extensive loss of the outer retinal elements in two patients. In addition, the subfoveal outer retinal layers may be partially preserved.
    CONCLUSIONS: Some veterinary anthelmintic drugs could be detrimental to the human retina if overdosed, resulting in visual disturbances. Optical coherence tomography revealed the mitochondria-enriched ellipsoid zone where outer retinal damage first appeared on, implying that these medications may harm the retina by inhibiting mitochondrial energy metabolism, as they do to eliminate parasites.
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  • 文章类型: Journal Article
    由于农药和兽药(P&VD)共存,植物衍生食品的污染风险尚未得到充分理解。随着越来越多的非法添加到食品中的意外P&VD,对于P&VDs的全面风险评估,必须开发一种非针对性的筛查方法。在这项研究中,基于高效液相色谱-串联质谱的结果,通过筛选合格变量来代表玉米中124个多类P&VDs的标记化合物,开发了一种改进的支持向量机(SVM)辅助代谢组学方法.主成分分析和正交偏最小二乘判别分析表明存在明显的组间差异,通过S-plot图进一步调查,置换测试,和变量在预测中的重要性,以获得合格的变量。同时,采用径向基函数下的SVM递归特征消除来获得从大到小的所有变量的权重平方值,以筛选合格的变量。进一步采用成对t检验和浓度的倍数变化来确认这些合格的变量以代表标记化合物。结果表明,通过SVM辅助代谢组学方法可以鉴定出124个P&VD中的120个,虽然仅通过代谢组学方法可以找到109个P&VD,这意味着支持向量机可以提高代谢组学方法的筛选准确性。此外,通过真实的污染玉米样品验证了该方法的实用性,在污染物的非靶向筛选方面具有广阔的应用前景。经计算,玉米样品中120个P&VDs的检出限为0.3~1.5μg/kg。
    The contamination risks of plant-derived foods due to the co-existence of pesticides and veterinary drugs (P&VDs) have not been fully understood. With an increasing number of unexpected P&VDs illegally added to foods, it is essential to develop a non-targeted screening method for P&VDs for their comprehensive risk assessment. In this study, a modified support vector machine (SVM)-assisted metabolomics approach by screening eligible variables to represent marker compounds of 124 multi-class P&VDs in maize was developed based on the results of high-performance liquid chromatography-tandem mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis indicate the existence of variables with obvious inter-group differences, which were further investigated by S-plot plots, permutation tests, and variable importance in projection to obtain eligible variables. Meanwhile, SVM recursive feature elimination under the radial basis function was employed to obtain the weight-squared values of all the variables ranging from large to small for the screening of eligible variables as well. Pairwise t-tests and fold changes of concentration were further employed to confirm these eligible variables to represent marker compounds. The results indicate that 120 out of 124 P&VDs can be identified by the SVM-assisted metabolomics method, while only 109 P&VDs can be found by the metabolomics method alone, implying that SVM can promote the screening accuracy of the metabolomics method. In addition, the method\'s practicability was validated by the real contaminated maize samples, which provide a bright application prospect in non-targeted screening of contaminants. The limits of detection for 120 P&VDs in maize samples were calculated to be 0.3~1.5 µg/kg.
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  • 文章类型: Journal Article
    农药/兽药不断向环境中引入,因此有必要对其对生态系统和人类健康的潜在风险进行快速评估。农药/兽药的发育毒性研究较少,更不用说对未经测试的农药的大规模预测了,兽药和生物农药。定量结构-活性关系(QSAR)等替代方法很有希望,因为它们具有确保这些化学品可持续和安全使用的潜力。我们收集了133种农药和兽药,以半最大活性浓度(AC50)作为斑马鱼胚胎发育毒性终点。QSAR模式的发展遵循严格的OECD原则,确保模型具有良好的内部稳健性(R2>0.6,QLOO2>0.6)和外部预测性(Rtest2>0.7,QFn2>0.7,CCCtest>0.85)。为了进一步增强模型的预测性能,使用RASAR和2D描述符的组合集建立了定量的结构-活性关系(q-RASAR)模型。力学解释表明,偶极矩,拓扑距离为10的C-O片段的存在,分子大小,亲脂性,基于欧氏距离(ED)的RA功能是影响毒性的主要因素。第一次,将已建立的QSAR和q-RASAR模型结合起来,优先考虑大量缺乏实验价值的真正外部化合物(农药/兽药/生物农药)的发育毒性.采用杠杆法和预测可靠性指标对各查询分子的预测可靠性进行评价。总的来说,双重计算毒理学模型可以为决策提供信息,并指导具有改进安全性的新农药/兽药的设计。
    The escalating introduction of pesticides/veterinary drugs into the environment has necessitated a rapid evaluation of their potential risks to ecosystems and human health. The developmental toxicity of pesticides/veterinary drugs was less explored, and much less the large-scale predictions for untested pesticides, veterinary drugs and bio-pesticides. Alternative methods like quantitative structure-activity relationship (QSAR) are promising because their potential to ensure the sustainable and safe use of these chemicals. We collected 133 pesticides and veterinary drugs with half-maximal active concentration (AC50) as the zebrafish embryo developmental toxicity endpoint. The QSAR model development adhered to rigorous OECD principles, ensuring that the model possessed good internal robustness (R2 > 0.6 and QLOO2 > 0.6) and external predictivity (Rtest2 > 0.7, QFn2 >0.7, and CCCtest > 0.85). To further enhance the predictive performance of the model, a quantitative read-across structure-activity relationship (q-RASAR) model was established using the combined set of RASAR and 2D descriptors. Mechanistic interpretation revealed that dipole moment, the presence of C-O fragment at 10 topological distance, molecular size, lipophilicity, and Euclidean distance (ED)-based RA function were main factors influencing toxicity. For the first time, the established QSAR and q-RASAR models were combined to prioritize the developmental toxicity of a vast array of true external compounds (pesticides/veterinary drugs/bio-pesticides) lacking experimental values. The prediction reliability of each query molecule was evaluated by leverage approach and prediction reliability indicator. Overall, the dual computational toxicology models can inform decision-making and guide the design of new pesticides/veterinary drugs with improved safety profiles.
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  • 文章类型: Journal Article
    复杂的食品基质严重限制了非目标分析中对潜在食品危害的一次性检测。因此,制定先进的样品预处理策略以减少基体效应具有重要意义。在这里,通过蚀刻核壳结构的COF,合成了具有大内部吸附容量和目标匹配孔径的新整合的中空结构共价有机骨架(HCOF)。制备的HCOF可直接用于蔬菜样品的基质清理,而聚多巴胺(PDA)网络的进一步修饰促进了动物样品的应用。HCOFs和HCOFs@PDA具有与基体干扰相当的尺寸,对目标物具有优异的吸附性能,在一次测试中对90种农药和44种兽药达到满意的回收率(70%-120%),分别。这项工作显示了具有高稳定性和定制尺寸的易于整合的HCOF在去除干扰基质方面的巨大潜力,并提供了一种通用策略,可以在高通量非目标分析中同时筛选大量危险。
    The complicated food matrix seriously limits the one-time test for the potential food hazards in non-targeted analysis. Accordingly, developing advanced sample pretreatment strategy to reduce matrix effects is of great significance. Herein, newly-integrated hollow-structured covalent organic frameworks (HCOFs) with large internal adsorption capacity and target-matched pore size were synthesized via etching the core-shell structured COFs. The as-prepared HCOFs could be directly applied for matrix clean-up of vegetable samples, while further modification of polydopamine (PDA) network facilitated application for animal samples. Both HCOFs and HCOFs@PDA with the comparable sizes to the matrix interference gave excellent adsorption performance to targets, achieving satisfied recoveries (70%-120%) toward 90 pesticides and 44 veterinary drugs in one-test, respectively. This work showed the great potential of the facile-integrated HCOFs with high stability and customized size to remove interference matrix and offered a universal strategy to achieve simultaneous screening of hazards with considerable quantity in high-throughput non-targeted analysis.
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  • 文章类型: English Abstract
    建立了同时检测12种禁用兽药的方法,包括β2受体激动剂,硝基呋喃代谢物,硝基咪唑,氯丙嗪,和氯霉素,在猪尿中。样品经酶解预处理,酸水解/衍生化,液-液萃取结合固相萃取。使用超高效液相色谱-串联质谱(UHPLC-MS/MS)进行检测。醋酸铵溶液(0.2mol/L,将4.5mL)和β-葡糖醛酸糖苷酶/芳基硫酸酯酶(40μL)添加到样品中,随后在37℃下酶解2小时。然后,向样品中加入1.5mL的1.0mol/L盐酸溶液和100μL的0.1mol/L邻硝基苯甲醛溶液。将混合物在37℃下孵育16小时,用8mL乙酸乙酯进行液液萃取。萃取后获得的下层水相使用混合阳离子交换固相萃取柱进行萃取和纯化。将提取物合并,用氮气吹干提取液,并将残留物重新溶解用于测定。在多反应监测模式下对样品进行分析,同时采用正电喷雾和负电喷雾电离,并使用同位素内标法进行定量。12个化合物的相关系数(r)均>0.99。氯霉素的检出限(LODs)和定量限(LOQs)分别为0.05和0.1μg/L,分别,其他化合物的LODs和LOQs分别为0.25和0.5μg/L,分别。在1、2和10倍LOQ时的平均回收率和RSD分别为83.6%-115.3%和2.20%-12.34%,分别。该方法灵敏度高,稳定性好,和准确的量化;因此,适用于猪尿中12种禁用兽药残留的同时测定。
    A method was established for the simultaneous detection of 12 prohibited veterinary drugs, including β2-receptor agonists, nitrofuran metabolites, nitroimidazoles, chlorpromazine, and chloramphenicol, in pig urine. The sample was pretreated by enzymolysis, acid hydrolysis/derivatization, and liquid-liquid extraction combined with solid-phase extraction. Detection was performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Ammonium acetate solution (0.2 mol/L, 4.5 mL) and β-glucuronidase/aryl sulfatase (40 μL) were added to the sample, which was subsequently enzymolized at 37 ℃ for 2 h. Then, 1.5 mL of 1.0 mol/L hydrochloric acid solution and 100 μL of 0.1 mol/L o-nitrobenzaldehyde solution were added to the sample. The mixture was incubated at 37 ℃ for 16 h, and the analytes were extracted with 8 mL of ethyl acetate by liquid-liquid extraction. The lower aqueous phase obtained after extraction was extracted and purified using a mixed cation-exchange solid-phase extraction column. The extracts were combined, the extraction solution was blow-dried with nitrogen, and the residue was redissolved for determination. The samples were analyzed under multiple-reaction monitoring mode with both positive and negative electrospray ionization, and quantified using an isotope internal standard method. The correlation coefficients (r) of the 12 compounds were >0.99. The limits of detection (LODs) and quantification (LOQs) of chloramphenicol were 0.05 and 0.1 μg/L, respectively, and the LODs and LOQs of the other compounds were 0.25 and 0.5 μg/L, respectively. The mean recoveries and RSDs at 1, 2, and 10 times the LOQ were 83.6%-115.3% and 2.20%-12.34%, respectively. The proposed method has the advantages of high sensitivity, good stability, and accurate quantification; thus, it is suitable for the simultaneous determination of the 12 prohibited veterinary drug residues in pig urine.
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  • 文章类型: English Abstract
    近年来,由于生产丰富和生活水平提高,禽蛋的消费量有所增加。因此,禽蛋的安全要求逐渐提高。目前,关于确定禽蛋产卵期间禁用兽药的分析方法的报道很少。因此,建立高通量和高效的筛选方法来监测产蛋期禁用的兽药势在必行。在这项研究中,开发了一种基于超高效液相色谱-串联质谱(UPLC-MS/MS)结合基于QuEChERS技术的分析方法,用于同时测定31种禁用的兽药,包括9种药物类别(大环内酯类,解热和镇痛药物,磺胺类药物,抗菌增效剂,抗球虫药,腐殖质,喹诺酮类药物,四环素,氨酚)在不同类型的禽蛋中。影响反应的主要因素,recovery,和方法的灵敏度,如提取溶剂,净化吸附剂,LC分离条件,和MS/MS参数,在样品预处理和仪器分析过程中进行了优化。用2mL0.1mol/L乙二胺四乙酸二钠溶液和8mL3%乙酸乙腈溶液提取2.00g鸡蛋中的31种兽药残留,并用2克氯化钠盐析。离心后,使用QuEChERS方法用100mg十八烷基硅烷键合的硅胶(C18)净化5mL上清液,50毫克的N-丙基乙二胺(PSA),和50mg的基于NH2的吸附剂。吹氮和再溶解后,在WatersCORTECSUPLCC18分析色谱柱(150mm×2.1mm,1.8μm)在流速下,柱温,注射量为0.4mL/min,30℃,和5μL,分别。在这些分析物中,在正电喷雾电离(ESI+)条件下,使用(A)5mmol/L乙酸铵(pH4.5)和(B)乙腈作为流动相,以动态多反应监测(MRM)模式获得26种分析物。梯度洗脱程序如下:0-2.0分钟,12%B-30%B;2.0-7.5分钟,30%B-50%B;7.5-10.0分钟,50%B;10.0-10.1分钟,50%B-100%B;10.1-12.0分钟,100%B;12.0-12.1分钟,100%B-12%B;使用(A)H2O和(B)乙腈作为流动相,在负电喷雾电离(ESI-)条件下以MRM模式获得其它五种目标分析物。梯度洗脱程序如下:0-2.0分钟,12%B-40%B;2.0-6.0分钟,40%B-80%B;6.0-6.1分钟,80%B-100%B;6.1-8.0分钟,100%B;8.0-8.1分钟,100%B-12%B使用基质匹配的外标校准进行定量。结果表明,各化合物在各自范围内具有良好的线性关系,相关系数>0.99。检测限(LODs)和定量限(LOQs)分别为0.3-3.0μg/kg和1.0-10.0μg/kg,分别。31种禁用兽药的平均回收率达到三个水平(LOQ,最大残留限值(MRL),禽蛋中的2MRL)介于61.2%至105.7%之间,相对标准偏差(RSD)为1.8%~17.6%。该方法用于30份市售禽蛋样品中禁用兽药的检测和分析。包括20个鸡蛋,5个鸭蛋,5个鹅蛋在一个鸡蛋中检测到恩诺沙星,含量为12.3μg/kg。该方法简单,经济,实用,并能够同时测定禽蛋中的多种禁用兽药。
    The consumption of poultry eggs has increased in recent years owing to the abundance of production and improvements in living standards. Thus, the safety requirements of poultry eggs have gradually increased. At present, few reports on analytical methods to determine banned veterinary drugs during egg-laying period in poultry eggs have been published. Therefore, establishing high-throughput and efficient screening methods to monitor banned veterinary drugs during egg-laying period is imperative. In this study, an analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combined with QuEChERS-based techniques was developed for the simultaneous determination of 31 banned veterinary drugs encompassing nine drug classes (macrolides, antipyretic and analgesic drugs, sulfonamides, antibacterial synergists, anticoccidials, antinematodes, quinolones, tetracyclines, amphenicols) in different types of poultry eggs. The main factors affecting the response, recovery, and sensitivity of the method, such as the extraction solvent, purification adsorbent, LC separation conditions, and MS/MS parameters, were optimized during sample pretreatment and instrumental analysis. The 31 veterinary drug residues in 2.00 g eggs were extracted with 2 mL of 0.1 mol/L ethylene diamine tetraacetic acid disodium solution and 8 mL 3% acetic acid acetonitrile solution, and salted out with 2 g of sodium chloride. After centrifugation, 5 mL of the supernatant was cleaned-up using the QuEChERS method with 100 mg of octadecylsilane-bonded silica gel (C18), 50 mg of N-propylethylenediamine (PSA), and 50 mg of NH2-based sorbents. After nitrogen blowing and redissolution, the 31 target analytes were separated on a Waters CORTECS UPLC C18 analytical chromatographic column (150 mm×2.1 mm, 1.8 μm) at a flow rate, column temperature, and injection volume of 0.4 mL/min, 30 ℃, and 5 μL, respectively. Among these analytes, 26 analytes were acquired in dynamic multiple reaction monitoring (MRM) mode under positive electrospray ionization (ESI+) conditions using (A) 5 mmol/L ammonium acetate (pH 4.5) and (B) acetonitrile as mobile phases. The gradient elution program was as follows: 0-2.0 min, 12%B-30%B; 2.0-7.5 min, 30%B-50%B; 7.5-10.0 min, 50%B; 10.0-10.1 min, 50%B-100%B; 10.1-12.0 min, 100%B; 12.0-12.1 min, 100%B-12%B; The five other target analytes were acquired in MRM mode under negative electrospray ionization (ESI-) conditions using (A) H2O and (B) acetonitrile as mobile phases. The gradient elution program was as follows: 0-2.0 min, 12%B-40%B; 2.0-6.0 min, 40%B-80%B; 6.0-6.1 min, 80%B-100%B; 6.1-8.0 min, 100%B; 8.0-8.1 min, 100%B-12%B. Matrix-matched external standard calibration was used for quantification. The results showed that all the compounds had good linear relationships within their respective ranges, with correlation coefficients of >0.99. The limits of detection (LODs) and quantitation (LOQs) were 0.3-3.0 μg/kg and 1.0-10.0 μg/kg, respectively. The average recoveries of the 31 banned veterinary drugs spiked at three levels (LOQ, maximum residue limit (MRL), and 2MRL) in poultry eggs ranged from 61.2% to 105.7%, and the relative standard deviations (RSDs) ranged from 1.8% to 17.6%. The developed method was used to detect and analyze banned veterinary drugs in 30 commercial poultry egg samples, including 20 eggs, 5 duck eggs, and 5 goose eggs. Enrofloxacin was detected in one egg with a content of 12.3 μg/kg. The proposed method is simple, economical, practical, and capable of the simultaneous determination of multiple classes of banned veterinary drugs in poultry eggs.
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  • 文章类型: Journal Article
    冠状病毒一直在畜牧业和公共卫生领域引起全球关注。然而,目前缺乏具有广谱抗病毒活性的有效药物来应对新出现的突变株或耐药性带来的挑战.此外,鉴定多靶点药物的方法也不足。氨肽酶N(APN)和3C样蛋白酶(3CLpro)代表了宿主定向和病毒定向策略的有希望的靶标,分别,开发针对各种冠状病毒的有效药物。在这项研究中,通过靶向这两种蛋白质,马德霉素铵表现出广谱抗病毒作用。来自两个靶蛋白配体的结合域4具有结构相似性,这表明筛选和设计基于这些领域的药物可能表现出广谱和高效的抗病毒活性。此外,已经确定聚醚离子载体携带锌离子的能力可能是它们能够靶向APN并表现出抗病毒作用的原因之一。本实验的发现为未来的药物筛选和设计提供了新的视角,同时也为聚醚离子载体在牲畜健康管理中的利用提供了有价值的参考。
    Coronaviruses have consistently posed a major global concern in the field of livestock industry and public health. However, there is currently a lack of efficient drugs with broad-spectrum antiviral activity to address the challenges presented by emerging mutated strains or drug resistance. Additionally, the method for identifying multitarget drugs is also insufficient. Aminopeptidase N (APN) and 3C-like proteinase (3CLpro) represent promising targets for host-directed and virus-directed strategies, respectively, in the development of effective drugs against various coronaviruses. In this study, maduramycin ammonium demonstrated a broad-spectrum antiviral effect by targeting both of the proteins. The binding domains 4 Å from the ligand of both target proteins shared a structural similarity, suggesting that screening and designing drugs based on these domains might exhibit broad-spectrum and highly effective antiviral activity. Furthermore, it was identified that the polyether ionophores\' ability to carry zinc ion might be one of the reasons why they were able to target APN and exhibit antiviral effect. The findings of this experiment provide novel perspectives for future drug screening and design, while also offering valuable references for the utilization of polyether ionophores in the management of livestock health.
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