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A multiclass method has been developed to screen and confirm a wide range of anti-microbial residues in muscle and milk, and validated using liquid-chromatography coupled to (low-resolution, LR) tandem mass spectrometry (LC-QqQ). Over sixty antibiotics, belonging to ten distinct families, were included in the method scope. The development process was rapidly concluded as a result of two previously implemented methods. This consisted of identical sample treatments, followed by liquid chromatography, and coupled with high-resolution (HR) mass spectrometry (LC-Q-Orbitrap). The validation study was performed in the range between 10−1500 μg·kg^−1 for muscles and 2−333 μg·kg^−1 for milk. The main performance characteristics were estimated and, then, compared to those previously obtained with HR technique. The validity of the method transfer was ascertained also through inter-laboratory studies.