High sensitive multiresidue analysis of pharmaceuticals and antifungals in surface water using U-HPLC-Q-Exactive Orbitrap HRMS. Application to the Danube river basin on the Romanian territory

<p>The occurrence of 67 pharmaceutical and antifungal residues in the Danube river on the Romanian territory was studied by using solid-phase extraction (SPE) and LC-Q Exactive Orbitrap high resolution MS in both full scan (FS) MS and targeted MS/MS modes. A single-laboratory validation procedure was carried out for the determination of 67 compounds in FSMS mode evaluating selectivity, sensitivity, linearity, precision and accuracy. The method showed satisfactory analytical performance. The evaluation of the recovery concluded that 75% of the compounds show recoveries between 85 and 115% and 10% of the compounds show recoveries between 85% and 65%. The level of detection was lower than 5ngl^-1 for 66% of the compounds, between 5 and 10ngl^-1 for 22% and between 10 and 25ngl^-1 for 14% of the compounds. The coefficients of determination R² were higher than 0.99 for 79% of the compounds, over a linearity range of 2.5-50ngl^-1. Targeted MS/MS analysis, performed in addition to the full scan acquisition was used for confirmatory purpose.Twenty samples of Danube water and three of the main tributaries were collected in May, July, August and October 2014. Analysis of the selected water samples revealed the occurrence of 23 compounds such as diclofenac, carbamazepine, sulfamethoxazole, tylosin, indomethacin, ketoprofen, piroxicam, together with antifungals like thiabendazole, and carbendazim. Carbamazepine was detected in 17 samples, the maximum concentration being 40ngl^-1. The highest concentration reached was 166ngl^-1 for diclofenac.</p

Ultrasonic or accelerated solvent extration followed by U-HPLC-high mass accuracy MS for screening of pharmaceuticals and fungicides in soil and plant samples

Different veterinary pharmaceuticals are used in agricultural livestock becoming a source of environment contamination. Furthermore, no regulation exists for the concentration limits of pharmaceuticals in soil or water. Monitoring programs for environment contamination with pharmaceuticals are needed, requiring new sensitive and selective screening methods. The present study focuses on developing a method for the simultaneous scanning of forty-two compounds (pharmaceuticals, azole biocides and fungicides) in soil and plant material samples. For extraction purposes the use of ultrasonic assisted and accelerated solvent extraction (ASE) were compared. The extract was purified and concentrated by applying a solid phase extraction step followed by ultra-high-performance-chromatographic separation and accurate-mass spectrometric detection using Exacte Orbitrap technology (FWHM 50,000). The effects of the different extraction solvents and conditions on the extraction efficiency were tested. Although both extraction approaches are applicable the optimal extraction efficiency was obtained by applying accelerated solvent extraction using solvent mixtures containing acetone for soil and methanol for plant samples. An ASE process has been validated for the determination of selected pharmaceuticals and fungicides in soil and in plant material. The recoveries from soil samples were >70% for more than 68% of the compounds. The levels of detection were =10 µg kg-1 for 93% of the compounds tested. The recoveries from plant material were >70% for 64% of the compounds tested. The levels of detection were =10 µg kg-1 for 66% of the compounds. The developed method was used to screen soil and plant material collected throughout the Netherlands and oxytetracycline residues were detected. -------------------------------------------------------------------------------

Accurate mass screening of pharmaceuticals and fungicides in water by U-HPLC-Exactive Orbitrap MS

The use of pharmaceuticals in livestock production is a potential source of surface water, groundwater and soil contamination. Possible impacts of antibiotics on the environment include toxicity and the emergence of antibiotic resistance. Monitoring programs are required to record the presence of these substances in the environment. A rapid, versatile and selective multi-method was developed and validated for screening 43 pharmaceutical and fungicides compounds, in surface and groundwater, in one single full-scan MS method, using benchtop U-HPLC-Exactive Orbitrap MS at 50,000 (FWHM) resolution. Detection was based on calculated exact masses and on retention time. Sample volume, pH conditions and solid-phase extraction (SPE) sample clean-up conditions were optimized. In the final method, 74 % of the compounds had recoveries higher than 80 %, 15 % of the compounds had recoveries between 60 % and 80 %, and 7 % of the compounds had recoveries between 40 % and 50 %. One of the compounds (itraconazole) had a recovery lower than 10 % and nystatin was not detected. The level of detection was 10 ng L-1 for 61 % of the compounds, 50 ng L-1 for 32 % and 100 ng L-1 for 5%. In-house validation, based on EU guidelines, proves that the detection capability CC beta is lower than 10 ng L-1 (for beta error 5 %) for 37 % of the compounds, lower than 50 ng L-1 for 35 % of the compounds and lower than 100 ng L-1 for 14 % of compounds. This study demonstrates that the ultra-high resolution and reliable mass accuracy of Exactive Orbitrap MS permits the detection of pharmaceutical residues in a concentration range of 10-100 ng L-1, applying a post target screening approach, in the multi-method conditions

Quantitative modelling to estimate the transfer of pharmaceuticals through the food production system

Use of pharmaceuticals in animal production may cause an indirect route of contamination of food products of animal origin. This study aimed to assess, through mathematical modelling, the transfer of pharmaceuticals from contaminated soil, through plant uptake, into the dairy food production chain. The scenarios, model parameters, and values refer to contaminants in emission slurry production, storage time, immission into soil, plant uptake, bioaccumulation in the animal's body, and transfer to meat and milk. Modelling results confirm the possibility of contamination of dairy cow's meat and milk due the ingestion of contaminated feed by the cattle. The estimated concentration of pharmaceutical residues obtained for meat ranged from 0 to 6 ng kg-1 for oxytetracycline, from 0.011 to 0.181 µg kg-1 for sulfamethoxazole, and from 4.70 to 11.86 µg kg-1 for ketoconazole. The estimated concentrations for milk were: zero for oxytetracycline, lower than 40 ng L-1 for sulfamethoxazole, and from 0.98 to 2.48 µg L-1 for ketoconazole. Results obtained for the three selected pharmaceuticals indicate a minor risk for human health. This study showed that supply chain modelling could be an effective tool in assessing the indirect contamination of feedstuff and animal products by residues of pharmaceuticals. The model can easily be adjusted to other contaminants and supply chain and, in this way, present a valuable tool to underpin decision making

Quantitative modelling to estimate the transfer of pharmaceuticals through the food production system

Use of pharmaceuticals in animal production may cause an indirect route of contamination of food products of animal origin. This study aimed to assess, through mathematical modelling, the transfer of pharmaceuticals from contaminated soil, through plant uptake, into the dairy food production chain. The scenarios, model parameters, and values refer to contaminants in emission slurry production, storage time, immission into soil, plant uptake, bioaccumulation in the animal's body, and transfer to meat and milk. Modelling results confirm the possibility of contamination of dairy cow's meat and milk due the ingestion of contaminated feed by the cattle. The estimated concentration of pharmaceutical residues obtained for meat ranged from 0 to 6 ng kg-1 for oxytetracycline, from 0.011 to 0.181 µg kg-1 for sulfamethoxazole, and from 4.70 to 11.86 µg kg-1 for ketoconazole. The estimated concentrations for milk were: zero for oxytetracycline, lower than 40 ng L-1 for sulfamethoxazole, and from 0.98 to 2.48 µg L-1 for ketoconazole. Results obtained for the three selected pharmaceuticals indicate a minor risk for human health. This study showed that supply chain modelling could be an effective tool in assessing the indirect contamination of feedstuff and animal products by residues of pharmaceuticals. The model can easily be adjusted to other contaminants and supply chain and, in this way, present a valuable tool to underpin decision making