Objective: To establish an HPLC method for the determination of potentially genotoxic impurity E, impurity I, and 2-chloromethyl-4-methoxy-3,5-dimethlpyridine in esomeprazole sodium. Methods: The chromatographic conditions were as follows: impurity E, YMC-Triart C18 column (250 mm×4.6 mm, 5 μm), mobile phase A 0.05 mol·L-1 monopotassium phosphate buffer, mobile phase B was acetonitrile, the gradient elution program was used at the flow rate of 1.0 mL·min-1, the detection wavelength was 302 nm and the column temperature was 30 ℃. Impurities I, Agilent Microspher C18 column (100 mm×4.6 mm, 3 μm), mobile phase A was water-phosphate buffer (pH 7.6)-acetonitrile(80:10:10), mobile phase B was acetonitrile-phosphate buffer (pH 7.6)-water (80:1:19), the flow rate was 1.0 mL·min-1, the detection wavelength was 302 nm and the column temperature was 30 ℃. 2-chloromethyl-4-methoxy-3,5-dimethlpyridine, GL Inertsil ODS-3 column (250 mm×4.6 mm, 5 μm), mobile phase A was 0.01 mol·L-1 disodium phosphate solution (pH 6.5), mobile phase B was acetonitrile, the flow rate was 1.0 mL·min-1, the detection wavelength was 265 nm and the column temperature was 30 ℃. Results: The linear ranges of impurity E, impurity I and 2-chloromethyl-4-methoxy-3,5-dimethlpyridine were 0.025 1-0.200 7, 0.020 2-0.302 7, 0.126 6-2.110 0 μg·mL-1. The LOQ of impurity E, impurity I, 2-chloromethyl-4-methoxy-3,5-dimethlpyridine were 0.50, 0.40, 2.53 ng, and the LOD were 0.15, 0.12, 0.84 ng. The average recovery rate ranged from 96% to 104%, and the RSD was less than 2%. No potential toxic impurities were detected in the samples. Conclusion: The method has the advantages of good repeatability, high precision, high accuracy and good linearity, and the analysis method are simple and efficient.
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