Stability Indicating Chromatographic Methods For Simultaneous Determination of Ceftriaxone Sodium and Sulbactam Sodium in their Combined Dosage Form

Abstract

Background: Two sensitive and accurate methods have been developed for the determination of ceftriaxone sodium and sulbactam sodium in presence of their acidic, alkaline, oxidative, neutral and photolytic degradation products by chromatography including TLC and HPLC methods, as stability- indicating techniques. Methods: The first one is RP-HPLC method based on isocratic elution of the two drugs with their degradation products using mobile phase consisting of 0.01 M potassium dihydrogen phosphate buffer (pH 4.6) – acetonitrile (94 : 6, v/v) with UV detection at 220 nm. In the second method, densitometric separation of the binary mixture of ceftriaxone, sulbactam and their degradation products was achieved using a developing system consisting of dichloromethane : methanol : isopropanol : n-butanol : ammonia 33 %: water (22.5 : 22.5 : 20 : 5 : 5 : 2.5, by volume) with ultra violet detection at 270 nm. The proposed methods were validated with respect to ICH guidelines and the structures of all degradation products of both drugs were elucidated for the first time by Fourier Transformed Infrared Spectroscopy (FTIR) and mass spectrometry. Results: Good recoveries 100.10 ± 0.14 and 100.03 ± 0.68 for ceftriaxone and 99.19 ± 0.33 and 100.78 ± 0.95 for sulbactam were obtained using HPLC and TLC methods, respectively. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the reported method and no significant differences were found. Conclusion: The proposed methods were successfully applied for the determination of ceftriaxone and sulbactam in pure form, in pharmaceutical preparations and in presence of their degradation products. Keywords: Ceftriaxone sodium, sulbactam sodium, degradation products, RP-HPLC, TLC, mass spectrometry.