The paper studies the process of analysis of tetracycline and paracetamol with the use of the HKUST-1 organometallic framework sorbent by high performance liquid chromatography. To obtain experimental data using the previously described technique, a sample of the material under consideration was synthesized and its physicochemical properties were studied. It has been established that individual sorbent particles have an octahedral shape and have a porous structure capable of adsorbing chemical compounds of various nature. The specific surface of the sample was calculated using the BET method and was Ssp = 551.3 m2/g. The study notes that when water or aqueous-organic media are used as eluents for chromatographic analysis, sorbents based on HKUST-1 have low stability; their degradation is observed when passing eluent solutions in an amount equal to 300-500 volumes of the chromatographic column. When only organic solvents are used for chromatographic analysis of tetracycline and paracetamol in the temperature range of 25-45 °C, no decomposition of the HKUST-1 sorbent and no degradation of the analyzed drugs are observed. Findings of research show that the efficiency of the eluent increases in the tetrahydrofuran-methanol-acetonitrile series. For all organic solvents used, the retention times were determined, the degree of separation, HETP, and the speed of response were calculated at various temperatures. A complex of studies has proved the possibility of using the organometallic sorbent HKUST-1 for the effective separation of drug mixtures by high-performance liquid chromatography. © 2020 Bauman Press. All rights reserved.