High resolution mass spectrometry screening method for routine surveillance of pharmacologically active substance...

This study presents the development and validation of a multi-residue screening method for the determination of 196 analytes in meat and milk using LC-Q-Orbitrap mass spectrometer in accordance with Commission Implementing Regulation (CIR) (EU) 2021/808. Four different multi-residue extraction methods from the literature were compared, and a double extraction combining an acetonitrile/water mixture followed by pure acetonitrile was selected as the most effective approach. The performance of the method showed good specificity for 87% of the target analytes. False negative results remained limited, affecting 6% of analytes in muscle and 8% in milk, and highlighting a few problematic compounds. The detection capability (CCβ) ranged from 5 to 10 µg/kg for 80% of the analytes in both matrices, whereas for the other substances CCβ values were found in the range of 50 to 100 µg/kg. In addition, the method fulfilled the quantification criteria of the CIR (EU) 2021/808 for 106 analytes in muscle and 115 analytes in milk at concentrations ranging from 5 µg/kg to 100 µg/kg. The method was further subjected to external evaluation through participation in different proficiency testing schemes for the determination of multi-class of VMPs. The results showed no false negatives and all obtained z-scores entered within the satisfactory range of ±2, proving that the method is suitable for both qualitative and quantitative screening of veterinary drug residues in animal-derived products and could be envisaged for somehow confirmatory status.