Multi-class, multi-residue analysis of trace veterinary drugs in milk by rapid screening and quantification using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry

A simple and rapid multi-class multi-residue analytical method was developed for the screening and quantification of veterinary drugs in milk by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). A total of 90 veterinary drugs investigated belonged to almost 20 classes including lincomycins, macrolides, sulfonamides, quinolones, tetracyclines, β-agonists, β-lactams, sedatives, β-receptor antagonists, sex hormones, glucocorticoids, nitroimidazoles, benzimidazoles, nitrofurans, and some others. A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure was developed for the sample preparation without the solid-phase extraction step. The linearity, sensitivity, accuracy, repeatability, and reproducibility of the method were fully validated. The response of the detector was linear for each target compound in a wide concentration range with a correlation coefficient (R2) of 0.9973 to 0.9999 (among them R2>0.999 for 73 of 90 analytes). The range of the limit of quantification for these compounds in the milk ranged from 0.10 to 17.30μg/kg. The repeatability and reproducibility were in the range of 2.11 to 9.62% and 2.76 to 13.9%, respectively. The average recoveries ranged from 72.62 to 122.2% with the RSD (n=6) of 1.30 to 9.61% at 3 concentration levels. For the screening method, the data of the precursor and product ions of the target analytes were simultaneously acquired under the all ions MS/MS mode in a single run. An accurate mass database for the confirmation and identification of the target compounds was established. The applicability of the screening method was verified by applying to real milk samples. The proposed analytical method allows the identification and confirmation of the target veterinary drugs at trace levels employing quick analysis time. Certain veterinary drugs were detected in some cases.