Improving the QuEChERS Liquid/Liquid Extraction of Analytes With Widely Varying Physicochemical Properties: Example of 201 Veterinary Drugs in Milk

QuEChERS is an extraction and sample processing technique widely used for multiresidue methods (e.g., pesticides or veterinary drugs).QuEChERS recovers a wide analyte polarity range, and yet low or even very low recoveries are observed for some polar analytes. This is especially relevant when analyzing veterinary drug residues in milk.Based on the Hoffmeister row, potassium hydrogenphosphate/dihydrogenphosphate were selected as salting-out agents. The methodology was termed p-QuEChERS.The avoidance of weak complexing agents (magnesium and probably sodium), as present in conventional QuEChERS salt mixtures, improved the partition of critical analytes into the organic phase. Significantly higher recoveries were obtained for analytes belonging to the families of tetracyclines, penicillins, and cephalosporins.The proposed p-QuEChERS concept, compared to conventional QuEChERS, improves the recovery of various polar analytes. Analytes benefiting from this methodology are drugs, which are particularly relevant in the specific field of multiresidue analysis in milk. On the other hand, none of the total 201 investigated analytes showed a reduced recovery. In addition, neither the sample handling nor the co-partition of involatile salts into the extracts was negatively affected.The p-QuEChERS based method has been fully validated according to European Community guidelines, using liquid chromatography coupled to high-resolution mass spectrometry instrumentation (time of flight (TOF) as well as Orbitrap). The developed multiresidue method quantifies 201 different veterinary drugs at relevant residue concentration in milk and is highly suitable for high throughput routine control.