Inter-laboratory study on analysis of veterinary medicinal product residues by liquid chromatography with triple quadrupole and/or high-resolution mass spectrometry in meat and milk matrices

A large-scale collaborative study, involving 32 laboratories worldwide, was conducted to evaluate the performances of low-resolution mass spectrometry (MS/MS) versus high-resolution mass spectrometry [(Q/)HRMS], both for identification and quantification of multi-class veterinary drug residues (amphenicols, cephalosporins, diaminopyrimidines, lincosamides, macrolides, penicillins, quinolones, sulfonamides, tetracyclines, avermectins, benzimidazoles, coccidiostats, NSAIDs). A total of 31 analytes of interest were selected and assessed in meat and milk from different species at or below established regulatory limits ranging from 10 to 200 ng/mL or from 5 to 100 ng/g tissue-equivalent. While both liquid chromatography MS detection techniques demonstrated overall effectiveness in the quantification of the analytes of interest, the results also highlighted challenges with both approaches. Penicillins were particularly challenging due to degradation issues, with frequent false positive and/or false negative issues for both instruments. A recurring source of false positives was the misidentification between ampicillin and cephalexin, especially in the case of MS/MS. A particular issue for (Q/)HRMS involved difficulties in the detection of ivermectin due to the non-optimized conditions used for its nontargeted data acquisition. Hydroxy-flunixin presented challenges in milk, especially for goat milk. Both MS/MS and (Q/)HRMS technologies were demonstrated to be useful for both qualitative and quantitative analysis, and the findings of this study underscore the importance of method optimization and careful data interpretation in multi-class veterinary drug analysis.