Determination of Polymerized in Cefotaxime Sodium and Cefotaxime Sodium for Injection by HPSEC / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a high performance size exclusion chromatography(HPSEC) method for the separation and analysis of polymers in cefotaxime sodium and cefotaxime sodium for injection, and determine the structures of the impurities by LCMS. METHODS: HPSEC was performed by using Sepax SRT SEC-150(7.8 mm × 300 mm, 5 μm) column. The mobile phase was 0.1 mol•L-1 disodium hydrogen phosphate and 0.1 mol•L-1 phosphate buffer solution. The flow rate was 0.8 mL•min-1, the detection wavelength was set at 235 nm, the injection volume was 10 μL, and the column temperature was maintained at 35 ℃. The concentration of polymers was quantified by external standard method. The LC-MS/MSn system conditions were as following the mobile phase was 20 mmol•L-1 amonium acetate, the flow rate was 0.8 mL•min-1, ESI source with positive and negative ion scan was utilized, the scanning range was m/z 200 - 1 600, and the post-column diversion ratio was 14. RESULTS: Eight impurity peaks were obtained in total; the resolutions were all greater than 1. 5. The linear range of cefotaxime was 1 - 100 μg•mL-1 (r = 1.000 0). The RSD repeatability was 1.2%(n = 6). The limit of detection was 0.2 μg and the limit of quantitation was 0.4 μg. Three polymers were identified by LC-MS. CONCLUSION: The HPSEC method can be used for the quantitative and qualitative analyses of individual polymer impurities. It is also sensitive for the control of polymers in cefotaxime.