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Their widespread use results in the contamination of the water environment, which, on the one hand, has a detrimental effect on aquatic organisms and, on the other hand, can lead to the emergence of resistant strains of microorganisms. All of the above determines the need for monitoring of these compounds in the environment, particularly, in water objects. Usually, the high\u2010performance liquid chromatography combined with tandem mass spectrometry method is used to solve this problem, however, this work shows the possibility of using the supercritical fluid chromatography\u2010tandem mass spectrometry method. An approach for the determination of four common macrolides, namely erythromycin, clarithromycin, midecamycin, and josamycin, was developed. The use of solid\u2010phase extraction allowed to achieve limits of quantification at 0.57\u20136.8\u00a0ng\/L. 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