Metabolomics reveals novel biomarkers of illegal 5-nitromimidazole treatment in pigs. Further evidence of drug toxicity uncovered.

The aim of the study was to investigate the potential of a metabolomics platform to distinguish between pigs treated with ronidazole, dimetridazole and metronidazole and non-medicated animals (controls), at two withdrawal periods (day 0 and 5). Livers from each animal were biochemically profiled using UHPLC-QTof-MS in ESI+ mode of acquisition. Several Orthogonal Partial Least Squares-Discriminant Analysis models were generated from the acquired mass spectrometry data. The models classified the two groups control and treated animals. A total of 42 ions of interest explained the variation in ESI+. It was possible to find the identity of 3 of the ions and to positively classify 4 of the ionic features, which can be used as potential biomarkers of illicit 5-nitroimidazole abuse. Further evidence of the toxic mechanisms of 5-nitroimidazole drugs has been revealed, which may be of substantial importance as metronidazole is widely used in human medicine.

Determination of imidocarb residues in bovine and ovine liver and milk by immunobiosensor.

Imidocarb (IMD) is a veterinary drug that has been used for more than 30 years to treat and prevent parasitic diseases. Pharmacokinetic studies have shown that substantial levels of IMD residues are retained in the edible tissues and milk of cattle and sheep for up to 6 months after administration. This has led to concern regarding the potential adverse effects posed through human consumption of edible tissue or milk from treated animals if the recommended withdrawal periods for the drug are not properly implemented. While MRLs have been established by the European Union, it is important that analytical methods are available to monitor food samples for potentially violative levels of IMD residues. A qualitative biosensor-based immunoassay was developed to allow the detection of IMD at less than the European Union MRLs of 50 µg kg(-1) for milk and 2 mg kg(-1) for bovine and ovine liver. Validation of the developed methods provided a detection capability of <25 µg kg(-1) in milk and <0.75 mg kg(-1) in liver. A comparison study was undertaken, with IMD incurred milk and ovine liver samples analysed by the newly developed procedures and results compared with those obtained by LC-MS/MS. The newly developed screening method was applied to both incurred milk and liver samples. This faster, cheaper and reliable screening method has potential use in sample analysis to ensure compliance with legislative requirements.

Determination of nitroxynil residues in tissues and bovine milk by immunobiosensor.

Nitroxynil is an anthelmintic drug mainly used for the control of liver fluke in sheep and cattle. The European Commission has established maximum residue limits in bovine and ovine muscle (400 µg kg(-1)), fat (200 µg kg(-1)), liver (20 µg kg(-1)) and kidney (400 µg kg(-1)), and more recently in bovine and ovine milk (20 µg kg(-1)). To ensure that these limits are not exceeded through incorrect use of the drug, it is necessary to monitor samples using robust and reliable methods capable of low-level detection. An inexpensive and rapid immunobiosensor-based screening procedure, capable of high sample throughput, was developed that is capable of detecting nitroxynil at <10 µg kg(-1) in bovine milk, at <10 µg kg(-1) in bovine liver, and at <200 µg kg(-1) in bovine and ovine muscle. The methods were fully validated and the milk assay was utilised in a comparison study of nitroxynil-incurred samples.