Objective: To establish an analytical method for polymer impurities in cefodizime sodium for injection. Methods: A YMC-pack ODS-A chromatographic column (150 mm×4.6 mm, 5 μm) was utilized with 0.01 mol · L-1 ammonium acetate solution-acetonitrile (950 ∶ 50) as mobile phase A and acetonitrile as mobile phase B, using gradient elution. Additionally, a TSKgel G2000SW chromatographic column (60 cm×7.5 mm, 10 μm) was used with phosphate buffer solution (pH 7.0)-acetonitrile (95 ∶ 5) as the mobile phase. These two chromatographic methods, along with a column-switching LC-MS method, were applied for the separation and structural elucidation of polymer impurities in samples with high polymer impurity content. The specificity of molecular exclusion chromatography for separating polymer impurities was also evaluated. A YMC-pack ODS-A column was used with phosphate buffer solution as mobile phase A and acetonitrile as mobile phase B, using gradient elution to detect polymer content. Results: Five polymer impurities with molecular weights between the main component and dimer were identified in cefodizime sodium bulk drug, self-made formulations, and reference formulations. Among them, four impurities had not been reported in literature, and no polymers larger than dimers were found. When using molecular exclusion chromatography to separate cefodizime sodium polymers, interference from small molecular impurities was observed, resulting in poor specificity. An RP-HPLC method was developed, capable of detecting all polymer impurities identified by molecular exclusion chromatography with good specificity. Using this method, the total polymer content was determined to be 0.26%. Conclusion: Molecular exclusion chromatography cannot effectively control polymer impurities in cefodizime sodium for injection. The established RP-HPLC method, with good specificity, can be used as an analytical method for routine quality control.
TU Hai-wei
,
YAN Ping
,
LI Qin-ze
,
YIN Dan
. Study on polymer impurities in cefodizime sodium for injection[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(4)
: 727
-738
.
DOI: 10.16155/j.0254-1793.2024-1292
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