Implant-based drug delivery necessitates a rigorous quantitative assessment and quality control of the drug release behavior. In this context, a fast simultaneous UV-VIS spectrometer quantification method was developed for an antibiotic dual drug system. Particular challenges arose from interfering spectra, as well as different solubility and stability of the drugs. The test system used here consists of the antibiotics Minocycline and Rifampin, which are used as an antibiotic combination approach in a growing number of device applications, such as impregnation of venous or urethral catheters. Two suitable wavelengths for this test system were identified. At a wavelength of 475 nm only Rifampin shows an absorption maximum, which was used to determine the concentration of Rifampin in the mixture. At 245 nm both antibiotics have a local extremum, a maximum for Minocycline, and a minimum for Rifampin. The developed UV-VIS spectrometer method for Rifampin and Minocycline dissolved in Sörensen buffer showed good results for small concentrations of Minocycline. For stability tests, a mixture of both antibiotics (1:1) was stored at 37°C for up to 144 h in NaCl solution (0.9%), and in Sörensen buffer, respectively. At defined time points, UV-VIS spectra were recorded, and feasibility of this quick simultaneous quantification method for these two widely used antibiotics was demonstrated.