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: News
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  • 文章类型: Journal Article
    背景:解决关键兽药,尤其是像阿苯达唑这样有溶解度问题的药物,以及它们对治疗效果的影响,体外溶出研究确实可以为不同品牌的阿苯达唑丸在标准化条件下的表现提供有价值的见解,有助于评估其溶出曲线和潜在的生物利用度。
    方法:从2020年12月至2021年5月收集了六个品牌的阿苯达唑300毫克大丸剂。实验室工作于2020年12月至2021年5月在国家动物产品和兽药和饲料质量评估中心(APVD-FQAC)实验室进行。从政府兽医诊所和私人兽医商店收集的品牌受到模型独立和依赖参数的影响。根据USP专论进行溶出试验。
    结果:研究发现,六个品牌均未达到溶出度测试的要求,因为根据USP标准,他们的API释放量在指定的60分钟时间内低于80%。模型独立性表明,只有一个品牌(Alb002=3.72)达到≤15%的差异因子。其余四个品牌(4/6)不符合此标准。然而,相似因子(f2)表明,所有五个品牌(5/6)都与比较产品相当,f2值为[公式:见文本]50%。平均溶出时间结果证实三个品牌(3/6)具有最高的溶出速率和最快的起效。模型依赖性动力学表明,Weibull和Korsemeyer-Peppas模型最适合药物的释放。
    结论:该研究突出了阿苯达唑丸剂的质量问题,强调需要进行国家体外溶出度研究。这些建议可以改善质量控制,简化监管框架,并提供实用的,评估药物疗效和安全性的经济有效方法,确保兽药符合安全和功效标准。
    BACKGROUND: Addressing critical veterinary drugs, especially drugs with solubility problems like albendazole, and their implications for therapeutic efficacy, in-vitro dissolution studies can indeed provide valuable insights into how different brands of albendazole boluses perform under standardized conditions, helping to assess their dissolution profiles and potential bioavailability.
    METHODS: Six brands of albendazole 300 mg boluses were collected from December 2020 to May 2021 G.C. The laboratory work was conducted from December 2020 to May 2021 in the National Animal Products and Veterinary Drugs and Feed Quality Assessment Centre (APVD-FQAC) laboratories. The collected brands from government veterinary clinics and private veterinary shops were subjected to model independent and dependent parameters. The dissolution test was conducted according to the USP monograph.
    RESULTS: The study found that none of the six brands met the requirements of the dissolution test, as their API release was less than 80% within the specified 60-minute timeframe according to USP standards. Model independence indicated that only one brand (Alb002 = 3.72) achieved a difference factor of ≤ 15%. The remaining four brands (4/6) did not meet this criterion. However, the similarity factor (f2) revealed that all five brands (5/6) were comparable to the comparator products, with f2 values of [Formula: see text]50%. The mean dissolution time results confirmed that three brands (3/6) had the highest dissolution rate and the fastest onset of action. The model-dependent kinetics indicated that the Weibull and Korsemeyer-Peppas models were the best fit for the release of drug substances.
    CONCLUSIONS: The study highlights issues with albendazole boluses\' quality, highlighting the need for national in-vitro dissolution studies. These recommendations could improve quality control, streamline regulatory frameworks, and offer practical, cost-effective methods for evaluating drug efficacy and safety, ensuring veterinary pharmaceuticals meet safety and efficacy standards.
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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
    在欧洲,用于饲料和食品目的的可食用昆虫的兴趣日益增加。需要有关化学危害从底物转移到幼虫的定量信息,以评估食品和饲料安全方面。当有机基质或诸如粪肥的残余流将用作基质时,尤其需要进行这种评估。促进循环食品系统。这项研究调查了兽药从加标底物向黑兵蝇幼虫(Hermetiaillucens)的转移。常用于鸡肉的兽药,育肥猪,和牛,并在粪便中定期检测到:三种不同的抗生素(恩诺沙星,土霉素,磺胺甲恶唑),三个抗球虫药(Narasin,盐霉素,toltrazuril)和一种抗寄生虫药物(eprinomectin)。将化学物质添加到昆虫底物中,使抗生素和抗寄生虫药物的终浓度达到0.5和5mg/kg,和5和50毫克/千克的球虫。黑兵蝇幼虫在加标基质上饲养1周,使用液相色谱和串联质谱法对兽药向幼虫和鱼尾的转移进行定量。只有土霉素和eprinomectin降低了黑兵蝇幼虫的平均体重和/或存活率。兽药向幼虫转移的土霉素平均占19.2%,12%的恩诺沙星,narasin为9.5%,eprinomectin的8.1%,盐霉素3.9%,4.2%的托曲齐利钠,和0.2%的磺胺甲恶唑,相对于底物中的浓度。质量平衡计算显示,幼虫似乎代谢兽药,事实上,恩诺沙星的代谢物,磺胺甲恶唑,在幼虫和frass中检测到了托曲唑。总之,应评估昆虫饲养基质是否存在兽药残留,以确保饲料(和食品)安全,以及对昆虫生长的可能影响。
    There is an increasing interest in edible insects in Europe for feed and food purposes. Quantitative information on the transfer of chemical hazards from substrates to larvae is needed to evaluate food and feed safety aspects. This evaluation is especially needed when organic substrates or residual streams such as manure will be applied as substrate, contributing to a circular food system. This study investigated the transfer of veterinary drugs from spiked substrate to black soldier fly larvae (Hermetia illucens). Veterinary drugs that are commonly administered to chicken, fattening pigs, and cattle and regularly detected in manure were included: three different antibiotics (enrofloxacin, oxytetracycline, sulfamethoxazole), three coccidiostats (narasin, salinomycin, toltrazuril) and one antiparasitic drug (eprinomectin). The chemicals were spiked to insect substrate to reach final concentrations of 0.5 and 5 mg/kg for the antibiotics and the antiparasitic drug, and 5 and 50 mg/kg for the coccidiostats. Black soldier fly larvae were reared for 1 week on the spiked substrates, and the transfer of the veterinary drugs to the larvae and frass was quantified using liquid chromatography coupled with tandem mass spectrometry. Only oxytetracycline and eprinomectin reduced the average weight and/or survival of the black soldier fly larvae. The transfer of the veterinary drugs to the larvae was on average 19.2% for oxytetracycline, 12% for enrofloxacin, 9.5% for narasin, 8.1% for eprinomectin, 3.9% for salinomycin, 4.2% for toltrazuril, and 0.2% for sulfamethoxazole, relative to concentrations in the substrate. Mass-balance calculations revealed that the larvae seem to metabolise veterinary drugs, and indeed, metabolites of enrofloxacin, sulfamethoxazole, and toltrazuril were detected in the larvae and frass. In conclusion, insect-rearing substrates should be evaluated for the presence of veterinary drug residues to ensure feed (and food) safety, as well as because of possible effects on insect growth.
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  • 文章类型: News
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  • 文章类型: Journal Article
    人类接触到与食物有关的和环境污染物的混合物,可能导致慢性疾病的病因。更好地表征“暴露体”是一项具有挑战性的任务,需要广泛的人类生物监测(HBM)。兽药(VD)/抗生素,在食品和动物生产中广泛使用和规范,然而,通常还没有包括在曝光组学工作流程中。因此,在这项工作中,先前建立的多分析物液相色谱-串联质谱(LC-MS/MS)方法涵盖了>80种不同的异源生物,并扩展了>40VDs/抗生素和农药。研究了通用工作流程是否允许在原理验证研究中成功整合大量新分析物。该扩展方法已成功进行了内部验证,并具有特异性,矩阵效应,线性度日内和日间精度,准确度,量化的极限,和检测进行了评估。优化的方法证明了在三个加标水平下具有可接受的RSD(<20%)的大多数添加的分析物的令人满意的回收率(81-120%)。大多数VDs/抗生素和杀虫剂(69%)显示出在50-140%范围内的基质效应。此外,灵敏度优异,中位数LOD和LOQs分别为0.10ng/mL和0.31ng/mL,分别。总的来说,扩展方法可用于在单次分析运行中检测和定量超过120种高度多样化的分析物。据作者所知,这项工作代表了第一个有针对性的生物监测方法,将VD与各种其他类别的污染物,包括增塑剂,PFAS,双酚,霉菌毒素,和个人护理产品。它证明了将靶向多分析物方法扩展到其他潜在有毒化学物质组的潜力。
    Humans are exposed to a cocktail of food-related and environmental contaminants, potentially contributing to the etiology of chronic diseases. Better characterizing the \"exposome\" is a challenging task and requires broad human biomonitoring (HBM). Veterinary drugs (VDs)/antibiotics, widely used and regulated in food and animal production, however, are typically not yet included in exposomics workflows. Therefore, in this work, a previously established multianalyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method covering >80 diverse xenobiotics was expanded by >40 VDs/antibiotics and pesticides. It was investigated if the generic workflow allowed for the successful integration of a high number of new analytes in a proof-of-principle study. The expanded method was successfully in-house validated and specificity, matrix effects, linearity, intra- and inter-day precision, accuracy, limits of quantification, and detection were evaluated. The optimized method demonstrated satisfactory recovery (81-120%) for most of the added analytes with acceptable RSDs (<20%) at three spiking levels. The majority of VDs/antibiotics and pesticides (69%) showed matrix effects within a range of 50-140%. Moreover, sensitivity was excellent with median LODs and LOQs of 0.10 ng/mL and 0.31 ng/mL, respectively. In total, the expanded method can be used to detect and quantify more than 120 highly diverse analytes in a single analytical run. To the best of the authors\' knowledge, this work represents the first targeted biomonitoring method integrating VDs with various other classes of pollutants including plasticizers, PFAS, bisphenols, mycotoxins, and personal care products. It demonstrates the potential to expand targeted multianalyte methods towards additional groups of potentially toxic chemicals.
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