In the European Union, the use of veterinary drugs belonging to the A6 group is prohibited in food-producing animals according to Commission Regulation (EU) No. 2010/37. The aim of this study was to ...improve the analytical control strategy by developing a single method to analyse residues of prohibited pharmacologically active substances in milk. For this, a single method was developed to analyse 16 prohibited pharmacologically active substances belonging to five different substance classes at required or recommended levels: nitroimidazoles at 3 μg kg
−1
, nitrofurans at 0.5 μg kg
−1
, chloramphenicol at 0.1 μg kg
−1
, dapsone at 5 μg kg
−1
and chlorpromazine at 1 μg kg
−1
. Milk sample preparation started with an acid hydrolysis combined with a derivatisation. These steps were followed by a clean-up consisting of a dispersive solid-phase extraction and a liquid-liquid extraction. Finally, the sample extracts were analysed by liquid chromatography combined with tandem mass spectrometry, operating alternately in the positive and negative mode. The method was fully validated according to Commission Decision 2002/657/EC for bovine milk and additionally validated for caprine milk. The validation proved that the method is highly effective to detect and confirm all 16 substances in bovine and caprine milk and, additionally to quantify 15 of these substances in bovine milk and 13 of these substances in caprine milk. This study resulted in a new multi-class method to detect, quantify and confirm the identity of 16 prohibited pharmacologically active substances belonging to five different substance classes in two types of milk.
It is generally accepted that the main route for human pharmaceuticals to the aquatic environment is via sewage treatment plants receiving wastewater from households and hospitals. We have analysed ...pharmaceuticals in the effluent from a wastewater treatment plant serving about 90 bulk drug manufacturers in Patancheru, near Hyderabad, India—a major production site of generic drugs for the world market. The samples contained by far the highest levels of pharmaceuticals reported in any effluent. The high levels of several broad-spectrum antibiotics raise concerns about resistance development. The concentration of the most abundant drug, ciprofloxacin (up to 31,000
μg/L) exceeds levels toxic to some bacteria by over 1000-fold. The results from the present study call for an increased focus on the potential release of active pharmaceutical ingredients from production facilities in different regions.
Aquaculture is a booming industry in the world and China is the largest producer and exporter of aquatic products. To prevent and treat diseases occurred in aquaculture, antibiotics are widely ...applied. However, the information of antibiotics used in Chinese aquaculture is still limited. Based on peer-reviewed papers, documents, reports, and even farmer surveys, this review summarized antibiotics used in Chinese aquaculture. In 2014, more than 47.4 million tonnes of farmed aquatic products were produced in mainland China. The outputs in the east and south parts of China can reach as much as 600 times higher than those in the northwest areas, which is clearly separated by the “Hu Line” – a line that marks a striking difference in the distribution of population. A total of 20 antibiotics belonging to eight categories have been reported for use, mainly via oral administration. However, only 13 antibiotics have been authorized for application in Chinese aquaculture and 12 antibiotics used are not authorized. Totally, 234 cases on antibiotic residues in Chinese aquatic products were recorded, including 24 fish species, eight crustacean species, and four mollusk species. Thirty-two antibiotics have been detected in aquatic products; quinolones and sulfonamides were the dominated residual chemicals. For specific compound, ciprofloxacin, norfloxacin, and sulfisoxazole have the highest concentrations. Except for a few cases, all residual concentrations were lower than the maximum residue limits. Through the consumption of aquatic products tainted by antibiotics, humans may acquire adverse drug reactions or antibiotic-resistant bacteria. However, the risk of antimicrobial resistance in human body, when exposed to antibiotics at sub-inhibitory concentrations, has not been exhaustively considered in the risk assessment. In addition, a national comprehensive investigation on the amount of antibiotics used in Chinese aquaculture is still needed in future studies.
Display omitted
•Present the distribution of aquaculture production and density in different regions of China.•Summary the varieties and doses of antibiotics used in Chinese aquaculture.•Clarify the occurrence and residues of antibiotics in aquatic products of China.•Examine the human health risk to antibiotics via consumption of aquatic products.
The usage, residue, potential human health risk of antibiotics in Chinese aquaculture were systematically summarized.
► A comprehensive study on the occurrence of antibiotics in eight STPs of Beijing. ► The antibiotics in STPs of Beijing are not eliminated completely. ► The antibiotics levels in sludge were higher ...in winter than other seasons. ► Total fluoroquinolones levels were lower than the PNEC for microorganisms.
The occurrence, removal efficiency and seasonal variation of 22 antibiotics, including eight fluoroquinolones, nine sulfonamides and five macrolides, were investigated in eight sewage treatment plants (STPs) in Beijing, China. A total of 14 antibiotics were detected in wastewater samples, with the maximum concentration being 3.1
μg
L
−1 in the influent samples and 1.2
μg
L
−1 in the effluent samples. The most frequently detected antibiotics were ofloxacin, norfloxacin, sulfadiazine, sulfamethoxazole, erythromycin and roxithromycin; of these, the concentration of ofloxacin was the highest in most of the influent and effluent samples. Eighteen antibiotics were detected in the sludge samples, with concentrations ranging from 1.0
×
10
−1 to 2.1
×
10
4
μg
kg
−1. The dominant antibiotics found in the sludge samples were the fluoroquinolones, with ofloxacin having the highest concentration in all the sludge samples. The antibiotics could not be removed completely by the STPs, and the mean removal efficiency ranged from −34 to 72%. Of all the antibiotics, the fluoroquinolones were removed comparatively more efficiently, probably due to their adsorption to sludge. Seasonal variation of the antibiotics in the sludge samples was also studied. The concentrations of antibiotics in winter were higher than in spring and autumn. Since the total levels of the fluoroquinolones detected in the influent samples were lower than the predicted no-effect concentration (PNEC) of 8.0
μg
L
−1, the residues of these antibiotics would be unlikely to have adverse effects on microorganisms involved in sewage treatment processes.
Penicillin G is a widely used antimicrobial in food-producing animals, and one of the most predominant drug residues in animal-derived food products. Due to reduced sensitivity of bacteria to ...penicillin, extralabel use of penicillin G is common, which may lead to violative residues in edible tissues and cause adverse reactions in consumers. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict drug residues in edible tissues and estimate extended withdrawal intervals for penicillin G in swine and cattle. A flow-limited PBPK model was developed with data from Food Animal Residue Avoidance Databank using Berkeley Madonna. The model predicted observed drug concentrations in edible tissues, including liver, muscle, and kidney for penicillin G both in swine and cattle well, including data not used in model calibration. For extralabel use (5× and 10× label dose) of penicillin G, Monte Carlo sampling technique was applied to predict times needed for tissue concentrations to fall below established tolerances for the 99th percentile of the population. This model provides a useful tool to predict tissue residues of penicillin G in swine and cattle to aid food safety assessment, and also provide a framework for extrapolation to other food animal species.
Display omitted
•A population PBPK model for procaine penicillin G in swine and cattle was developed.•The dissolution process of procaine penicillin G was incorporated into the model.•The model predicted drug concentrations in edible tissues well for swine and cattle.•The model can estimate withdrawal intervals after extralabel use of penicillin G.
•LC–MS/MS assay was developed and validated for determination of nitrofuran metabolites and nitroimidazole residues in honey.•Derivatisation of nitrofuran metabolites and a modified QuEChERS protocol ...were successfully employed.•The use of neat standard calibration curves in conjunction with a correction factor for matrix effect is presented.
LC–MS/MS assay was developed and validated according to EU guidelines for determination of nitrofuran metabolites and nitroimidazole residues in honey. Crude samples were acid-treated to liberate matrix-bound residues and a modified QuEChERS protocol was employed. Nitrofurantoin, furazolidone, furaltadone and nitrofurazone were determined via analysis of their metabolites AHD, AOZ, AMOZ and SEM, respectively while nitroimidazole residues; ronidazole (RNZ) and dimetridazole (DMZ) were determined directly. For all analytes, neat standard calibration curves, after correction for matrix effect were successfully employed. Decision limit (CCα) and detection capability (CCβ) were below the MRPL for nitrofurans (1.00μgkg−1) and the recommended concentration for nitroimidazole (3.00μgkg−1), respectively. The CCα, CCβ, percentage recovery and CV% ranges were 0.12–0.74μgkg−1, 0.21–1.27μgkg−1, 90.96–104.80% and 2.65–12.58%, respectively. This work is part of the national initiative for establishing a national monitoring program for drug residues in Egyptian honey.
A screening method for veterinary drug residues in fish, shrimp, and eel using LC with a high-resolution MS instrument has been developed and validated. The method was optimized for over 70 test ...compounds representing a variety of veterinary drug classes. Tissues were extracted by vortex mixing with acetonitrile acidified with 2% acetic acid and 0.2% p-toluenesulfonic acid. A centrifuged portion of the extract was passed through a novel solid phase extraction cartridge designed to remove interfering matrix components from tissue extracts. The eluent was then evaporated and reconstituted for analysis. Data were collected with a quadrupole-Orbitrap high-resolution mass spectrometer using both nontargeted and targeted acquisition methods. Residues were detected on the basis of the exact mass of the precursor and a product ion along with isotope pattern and retention time matching. Semiquantitative data analysis compared MS1 signal to a one-point extracted matrix standard at a target testing level. The test compounds were detected and identified in salmon, tilapia, catfish, shrimp, and eel extracts fortified at the target testing levels. Fish dosed with selected analytes and aquaculture samples previously found to contain residues were also analyzed. The screening method can be expanded to monitor for an additional >260 veterinary drugs on the basis of exact mass measurements and retention times.
Pharmaceutical and personal care products (PPCPs) are continuously introduced into the soil-plant system, through practices such as agronomic use of reclaimed water and biosolids containing these ...trace contaminants. Plants may accumulate PPCPs from soil, serving as a conduit for human exposure. Metabolism likely controls the final accumulation of PPCPs in plants, but is in general poorly understood for emerging contaminants. In this study, we used diclofenac as a model compound, and employed 14C tracing, and time-of-flight (TOF) and triple quadruple (QqQ) mass spectrometers to unravel its metabolism pathways in Arabidopsis thaliana cells. We further validated the primary metabolites in Arabidopsis seedlings. Diclofenac was quickly taken up into A. thaliana cells. Phase I metabolism involved hydroxylation and successive oxidation and cyclization reactions. However, Phase I metabolites did not accumulate appreciably; they were instead rapidly conjugated with sulfate, glucose, and glutamic acid through Phase II metabolism. In particular, diclofenac parent was directly conjugated with glutamic acid, with acyl-glutamatyl-diclofenac accounting for >70% of the extractable metabolites after 120-h incubation. In addition, at the end of incubation, >40% of the spiked diclofenac was in the non-extractable form, suggesting extensive sequestration into cell matter. The rapid formation of non-extractable residue and dominance of diclofenac-glutamate conjugate uncover previously unknown metabolism pathways for diclofenac. In particular, the rapid conjugation of parent highlights the need to consider conjugates of emerging contaminants in higher plants, and their biological activity and human health implications.
Display omitted
•A tiered approach involving 14C trace technique and liquid chromatography-high resolution mass spectrometry (LC-HRMS) was used to obtain a comprehensive fate of diclofenac in Arabidopsis (i.e. phase I, phase II, and phase III).•Target, suspect, and non-target analysis was multi-applied to identify the metabolites.•Eleven phase I and phase II metabolites were identified in Arabidopsis cells and validated in seedlings.•>40% non-extractable residue was observed in cells after 120-h incubation with diclofenac.•Acyl-glutamatyl-diclofenac was newly found phyto-transformation product of diclofenac.
Diclofenac was quickly metabolized by A. thaliana cells, resulting in a number of Phase I metabolites and Phase II conjugates, as well as Phase III non-extractable residue.
The honey bee, Apis mellifera, is frequently used as a sentinel to monitor environmental pollution. In parallel, general weakening and unprecedented colony losses have been reported in Europe and the ...USA, and many factors are suspected to play a central role in these problems, including infection by pathogens, nutritional stress and pesticide poisoning. Honey bee, honey and pollen samples collected from eighteen apiaries of western France from four different landscape contexts during four different periods in 2008 and in 2009 were analyzed to evaluate the presence of pesticides and veterinary drug residues.
A multi-residue analysis of 80 compounds was performed using a modified QuEChERS method, followed by GC-ToF and LC-MS/MS. The analysis revealed that 95.7%, 72.3% and 58.6% of the honey, honey bee and pollen samples, respectively, were contaminated by at least one compound. The frequency of detection was higher in the honey samples (n = 28) than in the pollen (n = 23) or honey bee (n = 20) samples, but the highest concentrations were found in pollen. Although most compounds were rarely found, some of the contaminants reached high concentrations that might lead to adverse effects on bee health. The three most frequent residues were the widely used fungicide carbendazim and two acaricides, amitraz and coumaphos, that are used by beekeepers to control Varroa destructor. Apiaries in rural-cultivated landscapes were more contaminated than those in other landscape contexts, but the differences were not significant. The contamination of the different matrices was shown to be higher in early spring than in all other periods.
Honey bees, honeys and pollens are appropriate sentinels for monitoring pesticide and veterinary drug environmental pollution. This study revealed the widespread occurrence of multiple residues in beehive matrices and suggests a potential issue with the effects of these residues alone or in combination on honey bee health.
Display omitted
•Fabric phase sorptive extraction-HPLC method developed for amphenicols in milk.•FPSE is a simple, fast, sensitive and green sample preparation approach.•FPSE eliminated protein ...precipitation step, reducing steps in sample preparation.•Sol–gel PEG coated FPSE media provided high efficiency extraction of amphenicols.•FPSE offers new capability to routinely monitor three amphenicols in milk samples.
A simple, sensitive, reliable, and fast analytical method was developed for the simultaneous determination of amphenicols residues in raw milk by combining fabric phase sorptive extraction (FPSE) and high-performance liquid chromatography-diode array detection. FPSE, a new generation green sample preparation technique, efficiently incorporates the advanced and tunable material properties of sol–gel derived microextraction sorbents with the rich surface chemistry of a cellulose fabric substrate, resulting in a flexible, highly sensitive, and fast microextraction device capable of extracting target analytes directly from complicated sample matrices. Due to the strong chemical bonding between the sol–gel sorbent and substrate, the microextraction device demonstrates a very high chemical and solvent stability. Therefore, any organic solvent/solvent mixture can be used as the eluent/back-extraction solvent.
Herein, a highly polar polymer coated FPSE media was created using short-chain poly(ethylene glycol) (PEG) and the applicability of this novel microextraction device to extract highly polar amphenicol antibiotics from raw milk was investigated. Due to the intense affinity of amphenicols towards the strongly polar sol–gel PEG-coated FPSE device, absolute recovery of the selected antibiotics residues were found to be 44% for thiamphenicol, 66.4% for florfenicol, and 81.4% for chloramphenicol. The developed method was validated in terms of sensitivity, linearity, accuracy, precision, and selectivity according to European Decision 657/2002/EC. Decision limit (CCα) values were 52.49μgkg−1 for thiamphenicol, 55.23μgkg−1 for florfenicol, and 53.8μgkg−1 for chloramphenicol, while the corresponding results for detection capability (CCβ) were 56.8μgkg−1, 58.99μgkg−1, and 55.9μgkg−1, respectively.
PDF
