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"veterinary drugs"
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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
by
Zweigenbaum, Jerry
,
Stevens, Joan
,
Anumol, Tarun
in
Agriculture
,
Analytical Chemistry
,
Animal food
2017
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
Journal Article
A randomised controlled trial to reduce highest priority critically important antimicrobial prescription in companion animals
by
Singleton, David A.
,
Pinchbeck, Gina L.
,
Noble, Peter-John M.
in
631/326/22/1290
,
692/700/565/1436/2774
,
706/689/2788
2021
Robust evidence supporting strategies for companion animal antimicrobial stewardship is limited, despite frequent prescription of highest priority critically important antimicrobials (HPCIA). Here we describe a randomised controlled trial where electronic prescription data were utilised (August 2018–January 2019) to identify above average HPCIA-prescribing practices (
n
= 60), which were randomly assigned into a control group (CG) and two intervention groups. In March 2019, the light intervention group (LIG) and heavy intervention group (HIG) were notified of their above average status, and were provided with educational material (LIG, HIG), in-depth benchmarking (HIG), and follow-up meetings (HIG). Following notification, follow-up monitoring lasted for eight months (April–November 2019; post-intervention period) for all intervention groups, though HIG practices were able to access further support (i.e., follow-up meetings) for the first six of these months if requested. Post-intervention, in the HIG a 23.5% and 39.0% reduction in canine (0.5% of total consultations, 95% confidence interval, 0.4-0.6,
P
= 0.04) and feline (4.4%, 3.4-5.3,
P
< 0.001) HPCIA-prescribing consultations was observed, compared to the CG (dogs: 0.6%, 0.5-0.8; cats: 7.4%, 6.0-8.7). The LIG was associated with a 16.7% reduction in feline HPCIA prescription (6.1% of total consultations, 5.3-7.0,
P
= 0.03). Therefore, in this trial we have demonstrated effective strategies for reducing veterinary HPCIA prescription.
Effective use of antimicrobials in both humans and animals is essential to help slow the emergence of antimicrobial resistance. Here, Singleton et al. present a randomised controlled trial demonstrating the efficacy of social norm messaging to reduce antibiotic prescription frequency in veterinary surgeries.
Journal Article
Nonmedical Uses of Antibiotics: Time to Restrict Their Use?
by
Piddock, Laura Jane Violet
,
Meek, Richard William
,
Vyas, Hrushi
in
Analysis
,
Animals
,
Anti-Bacterial Agents - toxicity
2015
The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted.
Journal Article
Simultaneous analysis of aminoglycosides with many other classes of drug residues in bovine tissues by ultrahigh-performance liquid chromatography–tandem mass spectrometry using an ion-pairing reagent added to final extracts
by
Lightfield, Alan R
,
Lehotay, Steven J
in
Aminoglycoside antibiotics
,
Aminoglycosides
,
Analytical chemistry
2018
The way to maximize scope of analysis, sample throughput, and laboratory efficiency in the monitoring of veterinary drug residues in food animals is to determine as many analytes as possible as fast as possible in as few methods as possible. Capital and overhead expenses are also reduced by using fewer instruments in the overall monitoring scheme. Traditionally, the highly polar aminoglycoside antibiotics require different chromatographic conditions from other classes of drugs, but in this work, we demonstrate that an ion-pairing reagent (sodium 1-heptanesulfonate) added to the combined final extracts from two sample preparation methods attains good separation of 174 targeted drugs, including 9 aminoglycosides, in the same 10.5-min ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis. The full method was validated in bovine kidney, liver, and muscle tissues according to US regulatory protocols, and 137–146 (79–84%) of the drugs gave between 70 and 120% average recoveries with ≤ 25% RSDs in the different types of tissues spiked at 0.5, 1, and 2 times the regulatory levels of interest (10–1000 ng/g depending on the drug). This method increases sample throughput and the possible number of drugs monitored in the US National Residue Program, and requires only one UHPLC–MS/MS method and instrument for analysis rather than two by the previous scheme.
Journal Article
Antimicrobial resistance in livestock and poor quality veterinary medicines
by
Clifford, Katie
,
Rahman, Tanvir
,
Islam, Taohidul
in
Agricultural production
,
Animals
,
Anti-Bacterial Agents - administration & dosage
2018
The annual market in Africa for substandard and non-registered veterinary medicine is estimated to be 400 million United States dollars,5 equal to that of the officially registered, quality-assured veterinary drug market.6 Numerous cases of antimicrobial resistance in humans have been traced to resistant microbes suspected of originating in livestock,7,8 which is particularly concerning as infected livestock can be asymptomatic.8 Transmission of resistant bacteria from livestock to humans can occur through the consumption of meat, direct contact with colonized animals or manure spread in the environment.7 The strongest correlation between interspecies pathogen transmission is observed in countries with policies to reduce agricultural antibiotic use. Poor-quality medicines that provide sub-therapeutic doses of active pharmaceutical ingredient, whether due to inadequate amounts of pharmaceutical, ineffective release, presence of impurities or degradation of compounds, are believed to contribute to antimicrobial resistance by exposing microbes to a level of antibiotic that will not effectively kill the whole microbial population.10 Poor-quality veterinary medicine as a contributor to antimicrobial resistance has been mentioned anecdotally in the literature, but systematic studies are lacking. Pharmaceutical quality is often assessed using high-performance liquid chromatography on field samples, an expensive, laboratory-based test that requires well-trained staff and a long waiting period for results.To sufficiently survey veterinary medicine quality in low- and middle-income countries, portable technologies that can provide quantitative information about the active pharmaceutical ingredient in an efficient and affordable manner are needed. The International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products programme develops global standards for veterinary medicine and helps countries establish drug registration protocols.15 The World Organization for Animal Health National Focal Point for Veterinary Products has established a network of global veterinary product experts, with each member nation represented by a local authority on veterinary health and medicine.16 Post-market identification Organizations concerned with antimicrobial resistance should work to raise awareness among government stakeholders in low- and middle-income countries about the issues surrounding poor-quality veterinary medicine, encouraging these countries to prioritize secure supply chains for veterinary medicine.
Journal Article
Comparison of analyte identification criteria and other aspects in triple quadrupole tandem mass spectrometry: Case study using UHPLC-MS/MS for regulatory analysis of veterinary drug residues in liquid and powdered eggs
2022
Ultrahigh-performance liquid chromatography (UHPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) is one of the most powerful tools for the multiclass, multiresidue analysis of veterinary drugs, pesticides, mycotoxins, and other chemical contaminants in foods and other sample types. Until approximately 2010, commercial MS/MS instruments using multiple reaction monitoring (MRM) were generally limited to minimum dwell (and inter-dwell) times of 10 ms per ion transition. To achieve the needed accuracy and detection limits for hundreds of targeted analytes, older UHPLC-MS/MS methods typically acquired only two ion transitions per analyte (yielding only one ion ratio for qualitative identification purposes), which is still the norm despite technological advancements. Newer instruments permit as little as 1 ms (inter-)dwell times to afford monitoring of more MRMs/analyte with minimal sacrifices in accuracy and sensitivity. In this study, quantification and identification were assessed in the validation of 169 veterinary drugs in liquid and powdered eggs. Quantitatively, an “extract-and-inject” sample preparation method yielded acceptable 70–120% recoveries and < 25% RSD for 139–141 (82–83%) of the 169 diverse drug analytes spiked into powdered and liquid eggs, respectively, at three levels of regulatory interest. Qualitatively, rates of false positives and negatives were compared when applying three different regulatory identification criteria in which two or three MRMs/drug were used in each case. Independent of the identification criteria, rates of false positives remained <10% for 95–99% of the drugs whether 2 or 3 ions were monitored, but the percent of drugs with >10% false negatives decreased from 25–45 to 10–12% when using 2 vs. 3 MRMs/analyte, respectively. Use of a concentration threshold at 10% of the regulatory level as an identification criterion was also very useful to reduce rates of false positives independent of ion ratios. Based on these results, monitoring >2 ion transitions per analyte is advised when using MS/MS for analysis, independent of SANTE/12682/2019, FDA/USDA, or 2002/657/EC identification criteria. (Quant)identification results using all three criteria were similar, but the SANTE criteria were advantageous in their greater simplicity and practical ease of use.
Journal Article
The Future of Antibiotics and Resistance: A Tribute to a Career of Leadership by John Bartlett
by
Spellberg, Brad
,
Gilbert, David N.
in
Agriculture
,
Animals
,
Anti-Bacterial Agents - pharmacology
2014
The ways we have developed, used, and protected antibiotics have led, predictably, to our current crisis of rising antibiotic resistance and declining new treatments. If we want to stave off a postantibiotic era, we need to fundamentally change our approach. We need to challenge long-standing assumptions and cherished beliefs. We need to push through the reflexive resistance and excuses (eg, \"that's not how we do things\" and \"that can't be done\") that result from challenging established ways. Excuses abound. Action is needed. Ultimately, we need a coordinated national action plan to combat resistance. Herein we discuss 7 tasks and 3 common themes that cut across those tasks, which are necessary to achieve long-term success in dealing with antibiotics and resistance. These principles derive from many years of dialogue with Dr John Bartlett. The field of infectious diseases, and indeed medicine in general, has benefited immeasurably from his remarkable leadership.
Journal Article
Comparison of four different multiclass, multiresidue sample preparation methods in the analysis of veterinary drugs in fish and other food matrices
2021
In 2018, AOAC International issued Standard Method Performance Requirements (SPMR) 2018.010 - Screening and Identification Method for Regulated Veterinary Drug Residues in Food. In response, we compared 4 different multiresidue methods of sample preparation using the same analytical method entailing ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Tilapia was chosen for testing, and the analytes and monitoring levels were from SPMR 2018.010. The methods consist of efficient procedures with published validation results from the US Department of Agriculture (USDA), Food and Drug Administration (FDA), and Canadian Food Inspection Agency (CFIA), and an enhanced-matrix removal (EMR)-Lipid protocol from China. Each method was used to prepare 102 final extracts of tilapia spiked or not at different levels with the 78 targeted analytes plus metabolites. The same FDA/USDA rules of mass spectral identification were employed in all analyses to assess rates of false positives and negatives. Quantitative accuracy of the methods was also compared in terms of recoveries and reproducibility of spiked tilapia, incurred catfish, and spiked and certified reference material of bovine muscle. Each method yielded generally acceptable results for the targeted veterinary drugs, but the USDA “extract & inject” method was the fastest, simplest, and cheapest to achieve equally or more acceptable results for the widest scope of analytes for the tested food matrices.
Journal Article
Evaluation of the antimicrobial use in pigs in Japan using dosage-based indicators
2020
The use of antimicrobial agents in food-producing animals may lead to the emergence and spread of antimicrobial resistance in bacteria of animal origin. The use of antimicrobial agents in pigs in 2018 in Japan was evaluated in terms of the weight of active ingredient and number of defined daily doses (DDD), using annual sales data of veterinary antimicrobials sold for use in pigs. In addition, the use of antimicrobial agents in the Japanese pig sector in 2008 to 2017 was evaluated to determine whether or not there were any differences in temporal change pattern by use of different metrics. In 2018, 447 metric tons of active ingredient, corresponding to 77,379 × 106 kg-days (Japanese DDD) and 34,903 × 106 kg-days (European DDD) were sold. The proportion of the sales amount of sulfonamides, trimethoprim and lincosamides to the total sales amount was significantly different depending on the metric used. For most antimicrobial classes, the number of Japanese DDDs was greater than the number of European DDDs. These results indicate that the DDD-based metric, which is more reflective of the selective pressure of antimicrobials, is recommended for use in monitoring the antimicrobial use in pigs in Japan. The differences in the number of Japanese DDDs and European DDDs appear to confirm the need for Japanese DDDs.
Journal Article