This work compares the electroanalytical performance of two electroanalytical systems based on (1) the glassy carbon electrode (GCE), and (2) the electrified liquid-liquid interface (eLLI), for the detection of fluoroquinolone antibiotic-danofloxacin (DANO). Our aim was to define the optimal conditions to detect the chosen analyte with two employed systems, extract a number of electroanalytical parameters, study the mechanism of the charge transfer reactions (oxidation at GCE and ion transfer across the eLLI), and to provide physicochemical constants for DANO. Detection of the chosen analyte was also performed in the spiked milk samples. To the best of our knowledge, this is the first work that directly compares the electroanalytical parameters obtained with solid electrode (in this case GCE) and eLLI. We have found that for DANO the latter provides better electroanalytical parameters (lower LOD and LOQ) as well as good selectivity when the milk was analyzed.

BACKGROUND: The presence of veterinary drug residues in food-producing animals and animal products is regulated through the enforcement of maximum residue limits (MRLs). To answer the need of the food sector to monitor these substances in a wide range of food commodities, stakeholders at AOAC INTERNATIONAL identified the need for a reliable confirmatory screening method. Such a qualitative approach is required for compliance checking and to support product release in manufacturing.
OBJECTIVE: Data were collected from five independent laboratories that applied the First Action Official Method 2020.04 to demonstrate adequate performance under reproducibility conditions. The probability of detection (POD) was calculated in blank test samples and test samples spiked at the screening target concentration (STC) level, with the objective to achieve PODs ≤10% and ≥90%, respectively. Additionally, the effectiveness of the screening method was evaluated by participating in 92 proficiency tests.
METHODS: Four streams were optimized to screen for 152 veterinary drug residues by LC-MS/MS in a wide variety of food commodities including milk-based ingredients and related products (e.g., milk fractions, infant formula, infant cereals, and baby foods), meat- and fish-based ingredients and related products (fresh, powdered, cooked, infant cereals, and baby foods), and other ingredients based on eggs, animal fat, and animal byproducts. The four streams covered 105 antibiotic residues, anti-inflammatory and antiparasitic agents (stream A), 23 beta-lactams (stream B), 14 aminoglycosides (stream C), and 10 tetracyclines (Stream D).
RESULTS: The multilaboratory validation led to PODs at the STC ≥94% and PODs in the blank ≤9%. Further application of the multilaboratory validated method to 92 proficiency tests provided more than 99% satisfactory submitted results (n = 784).
CONCLUSIONS: The interlaboratory reproducibility determined for this method met the acceptance criteria defined in AOAC Standard Method Performance Requirement (SMPR®) 2018.010.
CONCLUSIONS: AOAC has approved the method for Final Action status.

Brazil plays an important role in ensuring its position on the international market by assuring high food safety standards for its products, and all products should meet the requirements for residues from veterinary drugs and contaminants in animal products. Statutory monitoring provides insights into the compliance of the Brazilian industry regarding these legal requirements. The objective of this study was to provide insight into the safety of Brazilian animal products by reporting the occurrence of residues from veterinary drugs and contaminants according to an analysis of an 11-year report published by the Brazilian Ministry of Agriculture, Livestock and Food Supply (MAPA). Between 2010 and 2021, 166,647 samples from animal-derived products were analyzed in Brazil, and 624 of those samples were non-compliant (0.37%) exceeding maximum residue limits (>MRLs) or showed the presence of prohibited substances. The most common types of substances found in the non-compliant samples were heavy metals, parasiticides, and antimicrobials, accounting for 82% of all documents from the MAPA. Among Brazilian products, the challenge related to occurrence of substances varied across the food supply chain, with highest incidence rates observed in the fish chain, followed by eggs, milk, equids, sheep/goat, honey, bovine, swine, and broilers chains in decreasing order. Considering the type of substance, heavy metals were found to be more prevalent in fish products, mainly arsenic in wild fish. The prevalence of contaminants and heavy metals decreased, while that of veterinary drugs increased in Brazilian products from 2010 to 2021. From these results, it can be concluded that the number of accidental incidents including those associated with environmental contaminants decreased over the last decade, opposed to those involving human adversaries and deliberate illegal actions, such as the abuse of veterinary drugs, increased. Future monitoring plans need to take this paradigm shift into account.

The main objective of the research was to study the environmental \"price\" of the large-scale, milk production from a rarely known perspective, from the mapping of the estrogenic footprint (the amount of oestrus-inducer hormonal products, and the generated endoestrogens) in the resulting slurry in a dairy cow farm. These micropollutants are endocrine-disrupting chemicals (EDCs) and can be dangerous to the normal reproductive functions even at ng/kg concentration. One of them, 17ß-estradiol, has a 20,000 times stronger estrogenic effect than bisphenol-A, a widely known EDC of industrial origin. While most studies on EDCs are short-term and/or laboratory based, this study is longitudinal and field-based. We sampled the slurry pool on a quarterly basis between 2017 and 2020. Our purpose was testing the estrogenic effects using a dual approach. As an effect-based, holistic method, we developed and used the YES (yeast estrogen screen) test employing the genetically modified Saccharomyces cerevisiae BJ3505 strain which contains human estrogenic receptor. For testing exact molecules, UHPLC-FLD was used. Our study points out that slurry contains a growing amount of EDCs with the risk of penetrating into the soil, crops and the food chain. Considering the Green Chemistry concept, the most benign ways to prevent of the pollution of the slurry is choosing appropriate oestrus-inducing veterinary pharmaceuticals (OIVPs) and the separation of the solid and liquid parts with adequate treatment methods. To our knowledge, this is the first paper on the adaptation of the YES test for medicine and slurry samples, extending its applicability. The adapted YES test turned out to be a sensitive, robust and reliable method for testing samples with potential estrogenic effect. Our dual approach was successful in evaluating the estrogenic effect of the slurry samples.

Antimicrobial resistance (AMR) poses a significant threat in veterinary medicine due to the excessive and inappropriate use of antimicrobial agents, compromising the effectiveness of these drugs. To combat AMR, the collection of data on the consumption of antibiotics is paramount, as there is a well-established connection between antibiotic use and AMR in both humans and food-producing animals. Hence, the current study aimed to generate measurable data concerning the sales patterns of antimicrobial drugs used in animal treatment in Montenegro over a five-year period (from 2017 to 2021). Furthermore, the study aimed to compare these sales figures with the overall sales of antimicrobial veterinary medicine products (AMVMPs) during the same period, with particular emphasis on the utilization of critically important antimicrobials (CIAs) for human use. Data on AMVMPs consumption from 2017 to 2021 were expressed in euros and were sourced from the Institute for Medicines and Medical Devices of Montenegro (CInMED) annual reports, complying with the regulatory framework of the Law on Medicines in this country. Research results indicate that the sales of AMVMPs increased from 2017 to peak in 2019, followed by a stable decline of 21.79% in 2021. However, the portion of selected CIAs AMVMPs in total sales experienced a minor decline from 2017 to 2019, followed by a noticeable 6.11% increase from 2019 to 2021. In order to address AMR challenges, these findings emphasize the importance of enhancing surveillance and monitoring of veterinary antimicrobial use, as well as CIAs for human use.

Analyte stability is more commonly a confounding factor in analytical chemistry than many analysts recognize. In this study, we assessed the stability of 31 common veterinary drugs in water and final extracts of bovine (milk and kidney/liver) and chicken (muscle and egg) matrices. Two different sample preparation methods were evaluated for one-month storage of the final extracts at typical room, refrigerator, and freezer temperatures. Liquid chromatography - mass spectrometry (LC-MS) by triple quadrupole and high-resolution techniques was used for analysis of the extracts spiked at different relevant concentrations for general regulatory purposes (10-1000 ng/g sample equivalent). Comparison of results between two labs demonstrated that stable drugs (≤20% loss) at all tested conditions consisted of danofloxacin, enrofloxacin, florfenicol, flubendazole, hydroxy-flubendazole, flumequine, flunixin, 5-hydroxy-flunixin, lincomycin, and meloxicam. The tested drugs found to be the most unstable (>20% loss at room temperature within a matter of days) consisted of the β-lactams (ampicillin, cefalexin, cloxacillin, and penicillin G). Curiously, the following antibiotics (mostly macrolides) were apparently more stable in sample extracts than water: emamectin, erythromycin, ivermectin, lasalocid, monensin, tilmicosin, tulathromycin, and tylosin. Those and the other drug analytes (ciprofloxacin, doxycycline, florfenicol amine, 2-amino-flubendazole, oxytetracycline, sulfadiazine, sulfadimethoxine, sulfamethazine, and trimethoprim) were mostly stable for a month in refrigerated extracts, especially at higher concentrations, but not in all cases. In practice, freezer storage of extract solutions was found to be acceptable for at least a month, with a few exceptions.

A key component of efforts to identify the biological and drug-specific aspects contributing to therapeutic failure or unexpected exposure-associated toxicity is the study of drug-intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, relatively little information is available for similar evaluations in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in developing such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine-colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this canine-colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both the absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine-colonoid-derived monolayers and compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.

A method for the rapid analysis of multiclass residual veterinary drugs in poultry muscle, egg, and raw milk was validated in accordance with Japanese guidelines. Using LC-MS/MS, 20 veterinary drugs, including sulfonamides, coccidiostats, and macrolides were analyzed in one injection. Analytes were extracted from the samples with acetonitrile and then dehydrated and salted out using magnesium sulfate, trisodium citrate, and sodium chloride. This method was assessed by performing recovery tests of chicken muscle, duck muscle, egg, and raw milk spiked with 20 new target analytes at concentrations of 10 and 100 µg/kg. According to this method, 17 out of 20 target analytes satisfied the guideline criteria in chicken muscle and duck muscle, and all 20 target analytes met the criteria in egg and raw milk. The limit of quantification was less than MRLs for all analytes. Residues were detected in 4 out of 99 samples and analyzed using the validated method, finding that the levels of all residues were lower than the limits of quantification. These results suggest that continuous monitoring for a new trend of veterinary drugs is necessary.

Veterinary pharmaceuticals (VPs) residues may end up on the soil via manure, and from there can be transported to groundwater due to leaching. In this study an analytical framework to estimate the leaching potential of VPs at the national scale is presented. This approach takes soil-applied VPs concentrations, soil-hydraulic and soil-chemical properties, groundwater levels, sorption and degradation of VPs into account. For six commonly soil-applied VPs in the Netherlands, we assess quantities leached to groundwater and their spatial distribution, as well as the relative importance of processes that drive leaching. Our results for VPs Oxytetracycline, Doxycycline, and Ivermectin indicate that maximum quantities that may leach to groundwater are very low, i.e. ≪1 μg/ha, hence spatial differences are not investigated. For VPs Sulfadiazine and Flubendazole we identify a few regions that are potentially prone to leaching, with leached quantities higher than 1 μg/ha. Leaching patterns of these two VPs are dominated by soil properties and groundwater levels rather than soil-applied quantities. For Dexamethasone, even though applied on the soil in much lower concentrations compared to other investigated VPs, spatially widespread leaching to groundwater is found, with leached quantities higher than 1 μg/ha. Due to the leaching affinity of Dexamethasone, variations in the soil-applied amounts have significant influence on the quantities leached to groundwater. Dexamethasone is highlighted as important for the future environmental risk assessment efforts. This study has shown that the leaching potential of VPs is not determined by one single parameter, but by a combination of parameters. This combination also depends on the compound investigated.

In veterinary medicine, various drugs are used on a daily basis. Using inappropriate medications poses health hazards to companion animals and humans; thus, assessing adverse events in veterinary medicine has great social significance but remains an untapped area of research. In this study, to promote the appropriate use of veterinary drugs and clarify common pharmaceutical issues in Japanese veterinary medicine, we analyzed information in the Veterinary Drug Side Effects Database (National Veterinary Assay Laboratory of the Ministry of Agriculture, Forestry and Fisheries, Japan). We found that the number of reports has been increasing annually, including those on high-risk drugs, molecular-targeted drugs, and antibody-based drugs. The details of the reports were similar to those from the United States, including the misadministration of veterinary drugs to humans, improper drug management, and re-administering drugs with a history of side effects. Furthermore, 46.50% of all reports mentioned the administration of one or more drugs, with the highest number of concomitant drugs being 10. In addition, 37.78% of all reports described the use of drugs in manners deviating from the intended use indicated in the package insert. Therefore, to avoid adverse events, pharmacists may have to be involved in dispensing and aseptically preparing veterinary medicines and providing drug information and medication guidance. To optimize pharmacotherapy for ill companion animals, \"veterinary pharmacy\" and \"veterinary medicine pharmacy\" must be developed in line with clinical situations in Japan, while considering knowledge from countries that are advanced in terms of veterinary medicine.