Drug Residues In Animal-derived Foods Research Articles

Determination of 60 Food-Borne Stimulant Drug Residues in Animal-Derived Foods by Solid-Phase Extraction Purification and Ultra-High-Performance Liquid Chromatography-Quadrupole/Orbitrap High-Resolution Mass Spectrometry

A method for the rapid screening and confirmation of 60 food-borne stimulants in animal-derived foods was developed using the ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q/Orbitrap HRMS). After enzymatic hydrolysis at 37°C for 16 h, the samples were extracted with acetonitrile solution. The extraction solution was purified by PRiME HLB pass-through solid-phase extraction cartridge and redissolved by nitrogen blowing. The target compounds of reconstitution fluid were separated by Hypersil GOLD™ VANQUISH column (2.1 mm × 100 mm, 1.9 μm). The raw data were collected for the target compounds in Full Scan-ddMS2 mode, and then the Quan Browser module under Xcalibur software can be used to analyze the quantitative results of the samples. The combination of Tracefinder and mzVault software can realize the qualitative screening and confirmation of the samples. The results showed that the relative deviation of the exact mass of the 60 food-borne stimulants was less than 5.0 × 10−6, which had a good linear relationship in the corresponding concentration, and the correlation coefficient (R2) was greater than 0.9966. The detection limit ranged from 0.05 to 0.5 μg/kg. The quantification limit ranged from 0.1 to 1 μg/kg. The method recoveries ranged from 70.2% to 111.9% with relative standard deviations of 0.05% to 9.00% (n = 6). The method is easy to operate, covers a wide range of targets, and has high efficiency and accuracy. It is suitable for rapid screening and confirmation of various food-derived stimulants in animal-derived foods and provides assistance for food safety in the major events.

Antibody Production, Immunoassay Establishment, and Specificity Study for Flunixin and 5-Hydroxyflunixin.

Flunixin (FLU) is a nonsteroidal drug that is widely used in animals, causing severe drug residues in animal-derived foods and environment. The development of antibody-based rapid immunoassay methods is of great significance for the monitoring of FLU and its metabolite 5-hydroxyflunixin (5-FLU). We prepared monoclonal antibodies (mAbs) with different recognition spectra through FLU-keyhole limpet hemocyanin conjugates as immunogen coupled with antibody screening strategies. mAb5E6 and mAb6D7 recognized FLU with high affinity, and mAb2H5 and mAb4A4 recognized FLU and 5-FLU with broad specificity. Through evaluating the recognition of these mAbs against more than 11 structural analogues and employing computational chemistry, molecular docking, and molecular dynamics methodologies, we preliminarily determined the recognition epitope and recognition mechanism of these mAbs. Finally, an indirect competitive enzyme-linked immunosorbent assay for FLU based on mAb6D7 was developed, which exhibited limits of detection as low as 0.016-0.042 μg kg -1 (L-1) in milk and muscle samples.

Simultaneous quantitative determination of residues of abamectin, ivermectin, albendazole and its three metabolites in beef and chicken by HPLC-PDA.

Antimicrobial drugs are frequently used in a combination or shuttle way to cope with coinfection of bacteria or parasites and prevent drug resistance, thus the accurate quantification of multiple drug residues in animal-derived foods is crucial to ensure food safety. Here, a simple and efficient high-performance liquid chromatography-photodiode array (HPLC-PDA) method was established for the simultaneous quantitative screening of six common residues of antiparasitic drugs, including abamectin (ABM), ivermectin (IVM), albendazole (ABZ) and the three metabolites of ABZ in beef and chicken. The LODs and LOQs for six target compounds in beef and chicken are determined to be 3.2 to 12.5µg/kg and 9.0 to 30.0µg/kg, respectively. The calibration curves show good linearity (R2≥0.9990) between the peak area and concentration. The recoveries from the fortified blank samples are all above 85.10%. Finally, the applicability of the HPLC-PDA method is successfully demonstrated by the real sample analysis.

A Review of Veterinary Drug Residue Detection: Recent Advancements, Challenges, and Future Directions

Veterinary drug residues of common food (milk, meat) have posed serious threats to the environment and human health, making the quality and safety of agricultural, livestock, and aquatic products increasingly prominent. With the widespread use of veterinary drugs and the requirements for food safety, it has become urgent to detect veterinary drug residues in animal-derived foods. So far, few studies have systematically reviewed the progresses, challenges, and future directions in veterinary drug residue detection. A thorough review on the current advancements, challenges, and potential future directions of veterinary drug residue detection will be extremely beneficial and timely. This study reviewed recent developments of detection technology of veterinary drug residues. The current issues and challenges in veterinary drug residue detection were examined and highlighted. Finally, future proposals on directions and prospects for veterinary drug residue detection were suggested. High-throughput and high-sensitivity veterinary drug detection technology, sample pretreatment technology for rapid processing, and the fusion of multiple detection methods were recommended as the main directions for the future development of veterinary drug residue detection. It was suggested to develop the analysis and detection technologies of veterinary drug residue towards high automation, high sensitivity, and high throughput in the future. This review provides new ideas and strategies for the rapid development of animal husbandry industry and protecting consumers’ physical health and food safety.

Evaluation of Antibiotics Residues in Milk and Meat Using Different Analytical Methods.

Veterinary drugs are pharmacologically and biologically active chemical agents. At present, veterinary drugs are extensively used to prevent and treat animal diseases, to promote animal growth, and to improve the conversion rate of feed. However, the use of veterinary drugs in food-producing animals may leave residues of the parent compounds and/or their metabolites in food products resulting in harmful effects on humans. To ensure food safety, sensitive and effective analytical methods have been developing rapidly. This review describes sample extraction and cleanup methods, and different analytical techniques are used for the determination of veterinary drug residues in milk and meat. Sample extraction methods, such as solvent extraction, liquid-liquid extraction, and cleanup methods such as dispersive solid-phase extraction and immunoaffinity chromatography, were summarized. Different types of analytical methods such as microbial, immunological, biosensor, thin layer chromatography, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry were discussed for the analysis of veterinary drug residues in animal-derived foods. Liquid chromatography-tandem mass spectrometry is the most widely used analytical technique for the determination of antibiotic drug residues. This is due to the powerful separation of LC and accurate identification of MS, and LC-MS/MS is more popular in the analysis of veterinary drug residues.

Veterinary drug residues in animal-derived foods: occurrence, veterinary legislation and perceived risk factors in Cameroon

The presence of veterinary drug residues in animal-derived foods (ADF) remains a public health concern in low-income countries such as Cameroon. This paper provides an overview of the current status of antimicrobial (AM) residues in ADF, veterinary legislation on the use of AM and perception of risk factors with emphasis on the need for sustainable management in Cameroon from a one health perspective. Results show that a wide range of antimicrobials is used in the country with little or no attention to good veterinary practices. Residues of commonly used AM agents including those banned for use in food animal production in high-income countries were reported. The current legislation on the use of veterinary drugs is weak and does not make provision for key concepts such as Maximum Residue Limit. Veterinarians argue that the lack of disease diagnostic facilities and excessive use of AM has led to the presence of residues in ADFs. The government and relevant agencies need to enforce regulations for the use of veterinary drugs. Further, awareness creation through educational campaigns for users and consumers as well as the implementation of measures to restrict prescription and dispensation of AM agents to recognised veterinarians are necessary. More studies on AM residues in ADFs are needed to support veterinary drug surveillance policies. This paper strongly suggests collaboration between food safety experts, animal and human health professionals as well as policymakers to help implement good surveillance of antimicrobial use and to safeguard potent AM suitable for disease control for forthcoming generations.

Veterinary Drug Residues in Animal-Derived Foods: Sample Preparation and Analytical Methods.

Veterinary drugs are used to treat livestock and aquatic diseases and thus are introduced into animal-derived foods, endangering consumer health and safety. Antibiotic resistance is rapidly becoming a major worldwide problem, and there has been a steady increase in the number of pathogens that show multi-drug resistance. Illegal and excessive use of veterinary drugs in animals and aquaculture has serious adverse effects on humans and on all other environmental organisms. It is necessary to develop simple extraction methods and fast analytical methods to effectively detect veterinary drug residues in animal-derived foods. This review summarizes the application of various sample extraction techniques and detection and quantification methods for veterinary drug residues reported in the last decade (2010-2020). This review compares the advantages and disadvantages of various extraction techniques and detection methods and describes advanced methods, such as those that use electrochemical biosensors, piezoelectric biosensors, optical biosensors, and molecularly imprinted polymer biosensors. Finally, the future prospects and trends related to extraction methods, detection methods and advanced methods for the analysis of veterinary drug residues in animal-derived foods are summarized.

Determination of veterinary drug residues in food of animal origin: Sample preparation methods and analytical techniques

Veterinary drugs are widely used in animal husbandry to prevent and treat animal diseases, to promote animal growth, and to improve the conversion rate of feed. However, the use of veterinary drugs in food-producing animals may leave residues of the parent compounds, and/or their metabolites in food products resulting in harmful effects to humans. To ensure food safety, sensitive and effective analytical methods have been developing rapidly. So it is necessary to make a systematic summary of detection methods of veterinary drug residues. Sample preparation methods and analytical techniques are the two main parts of analyzing veterinary drug residues which were described in detail. Sample preparation methods, such as solid-phase extraction, liquid–liquid extraction, immunoaffinity chromatography, and QuEChERS, were summarized by the specific examples. The three types of methods, microbial, immunological, and physicochemical methods, for screening or determination were described, including microbial inhibition, enzyme-linked immunosorbent assay, colloidal gold immunoassay, fluorescence polarization immunoassay, biosensor technology, application of quantum dots, capillary electrophoresis, liquid chromatography, and liquid chromatography-mass spectrometry. In addition, the advantages and shortcomings of methods were also described. The challenges and prospects were discussed for the analysis of veterinary drug residues in animal-derived foods.

Antimicrobial drug residues in animal-derived foods: Potential impact on the human intestinal microbiome.

The use of veterinary drugs in food-producing animals may result in the presence of low levels of drug residues in these edible, animal-derived foods, with potential dietary exposure to humans. Since therapeutic doses of antibiotics have been shown to affect bacterial populations in the gastrointestinal tract microbiome and can also promote the emergence of antibiotic-resistant bacteria, there is concern that animal drugs at residue level concentrations could also perturb the intestinal microbiome composition and modify the antimicrobial resistance profile of the human intestinal microbiota. This review provides updated information on the VICH GL#36(R2), on evaluating the safety of veterinary drug residues in animal-derived foods and their effects on the human intestinal microbiome; discusses critical research knowledge gaps and challenges in evaluating the impact of drug residues in animal-derived foods on the human intestinal microbiome; and analyzes integrated basic and applied research approaches, currently being conducted at FDA, on studies that specifically address key regulatory science questions. Moreover, this review aims to emphasize future research needs on scientific methodology and provides general recommendations on drug inactivation, bioavailability, and antimicrobial resistance, to improve the safety evaluation and risk assessment of antimicrobial residues and their impact on the gastrointestinal microbiota, with the goal of ensuring food safety.

Comparison of veterinary drug residue results in animal tissues by ultrahigh-performance liquid chromatography coupled to triple quadrupole or quadrupole-time-of-flight tandem mass spectrometry after different sample preparation methods, including use of a commercial lipid removal product.

Veterinary drug residues in animal-derived foods must be monitored to ensure food safety, verify proper veterinary practices, enforce legal limits in domestic and imported foods, and for other purposes. A common goal in drug residue analysis in foods is to achieve acceptable monitoring results for as many analytes as possible, with higher priority given to the drugs of most concern, in an efficient and robust manner. The U.S. Department of Agriculture has implemented a multiclass, multi-residue method based on sample preparation using dispersive solid phase extraction (d-SPE) for cleanup and ultrahigh-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ) for analysis of >120 drugs at regulatory levels of concern in animal tissues. Recently, a new cleanup product called "enhanced matrix removal for lipids" (EMR-L) was commercially introduced that used a unique chemical mechanism to remove lipids from extracts. Furthermore, high-resolution quadrupole-time-of-flight (Q/TOF) for (U)HPLC detection often yields higher selectivity than targeted QQQ analyzers while allowing retroactive processing of samples for other contaminants. In this study, the use of both d-SPE and EMR-L sample preparation and UHPLC-QQQ and UHPLC-Q/TOF analysis methods for shared spiked samples of bovine muscle, kidney, and liver was compared. The results showed that the EMR-L method provided cleaner extracts overall and improved results for several anthelmintics and tranquilizers compared to the d-SPE method, but the EMR-L method gave lower recoveries for certain β-lactam antibiotics. QQQ vs. Q/TOF detection showed similar mixed performance advantages depending on analytes and matrix interferences, with an advantage to Q/TOF for greater possible analytical scope and non-targeted data collection. Either combination of approaches may be used to meet monitoring purposes, with an edge in efficiency to d-SPE, but greater instrument robustness and less matrix effects when analyzing EMR-L extracts. Graphical abstract Comparison of cleanup methods in the analysis of veterinary drug residues in bovine tissues.

Human Food Safety Implications of Variation in Food Animal Drug Metabolism.

Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug- and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs.

Multicomponent mesofluidic system for the detection of veterinary drug residues based on competitive immunoassay

An automated multicomponent mesofluidic system (MCMS) based on biorecognitions carried out on meso-scale glass beads in polydimethylsiloxane (PDMS) channels was developed. The constructed MCMS consisted of five modules: a bead introduction module, a bioreaction module, a solution handling module, a liquid driving module, and a signal collection module. The integration of these modules enables the assay to be automated and reduces it to a one-step protocol. The MCMS has successfully been applied toward the detection of veterinary drug residues in animal-derived foods. The drug antigen-coated beads ( ϕ 250 μm) were arrayed in the PDMS channels ( ϕ 300 μm). The competitive immunoassay was then carried out on the surface of the glass beads. After washing, the Cy3-labeled secondary antibody was introduced to probe the antigen–antibody complex anchored to the beads. The fluorescence intensity of each bead was measured and used to determine the residual drug concentration. The MCMS is highly sensitive, with its detection limits ranging from 0.02 (salbutamol) to 3.5 μg/L (sulfamethazine), and has a short assay time of 45 min or less. The experimental results demonstrate that the MCMS proves to be an economic, efficient, and sensitive platform for multicomponent detection of compound residues for contamination in foods or the environment.

Human Health Risks Associated with Drug Residues in Animal-Derived Foods

Adulteration of food supply by agricultural chemicals has gained national attention as a potential health hazard. Public fears over chemical residues in foods do not appear commensurate with the risks established through experimental or epidemiologic studies. This paper examines the risk to human health from consumption of drug residues in animal-derived foods. In particular, it focuses on antimicrobial residues and residues of natural and synthetic hormones used to enhance the growth of livestock. In addition, the paper addresses the disastrous consequences to public health when safe and effective veterinary drugs are banned from use because of socioeconomic considerations.