This study showed the comparison of UV spectroscopy and High Performance Liquid Chromatography (HPLC) for ceftriaxone stability. UV spectroscopy using wavelength ratio between 241 and 271 nm absorbance values can be used successfully as a screening technique in ceftriaxone stability investigations. Ion paring reversed phase – High Performance Liquid Chromatography provided more precise stability characterization. The HPLC conditions developed were in isocratic mode using an YMC ODS H80, 150 x 4.6 mm, 4 μm with a mobile phase composed by 40% of methanol and 60% of phosphate buffer (10 mM; pH 7.5) where tetrabutylammonium bromide was solubilized at 18 mM. Detection was performed with a diode array detector from 200 to 400 nm. Sample injection volume was at 5 μL. Methanol was selected because better symmetry of ceftriaxone peak than acetonitrile was obtained. Both methods were validated. The calibration curve and stability study was performed over a concentration range of 7.5 to 16.5 mg.L-1. 100% corresponded to the concentration of 15 mg.L-1. Intermediate precision was tested on 6 independent samples at concentrations corresponding to 100% (15 mg.L-1) on 6 consecutive days. These values were within the acceptance criteria of 2% and showed that both methods were precise. Accuracy of the method was evaluated analyzing three independent samples at concentrations corresponding to 100%. Recovery percentage calculated between the known concentration and the calculated concentration of ceftriaxone showed that the methods were accurate. Thus both methods were linear. The stability study was performed at 40°C as infants with sepsis are generally febrile. Over the rectal pH range recorded in sick infants, the stability of ceftriaxone was maximal at pH 7.5. Over 6 hours in a pH range of 6.5 to 8.5 less than 10% of ceftriaxone is degraded. However at pH 5.5, degradation occurred more rapidly and loss of drug was significant.