This work aimed to determineof Ceftriaxone sodium (CFT) through the development and verification of a accurate and rapid isocratic of RP-HPLC method using a C18 as stationary phase column. The mobile phase was described as a mixture of 80:20 (5.8 -8) Buffer:methanol. The optimum conditions for estimation were; column temperature 30 °C and flow rate of 0.7 mL/min. by using the UV-detection at a 241nm wavelength. The analysis data showed that the determination coefficient, R2 was 0.9985, detectioin limit of 4.3 x 10−6 µg/mL and limit of quantification of 1.4 x 10−5 µg/mL. This developed method was successfully examined for the estimate of ceftriaxone sodium in their pure form and in numeral commercial pharmaceuticals preparations with little interference of additives.