The intricate interplay between antibiotics and transition metal ions play an important role in drug distribution and efficacy. This study explores the interaction between two commonly used antibiotics, cefuroxime and amoxicillin, with transition metal ions. The complexes formed between these antibiotics and Zn ( II), Mn ( II), Co ( II), and Fe ( II) ions were synthesized and characterized using using High-Performance Liquid Chromatography (HPLC), UV-Vis spectrometry, and Fourier-Transform Infrared spectroscopy (FTIR). FTIR  spectra confirmed the formation of metal-antibiotic complexes. HPLC results revealed changes in retention time for complexes compared to individual antibiotics, while UV-Vis spectra also showed peak shift for these complexes. This study provides insights into the behavior of drugs in presence of transition metal ions for understaning drug distribution of these antibiotics.