OBJECTIVE  To establish an HPLC method for the determination of related substances in gefitinib tablets, so as to provide data support for the quality control and evaluation of the product.

METHODS  The separation was performed on a Shimadazu GL Inertsustain C₁₈(3.0 mm×100 mm, 3 μm) column, mobile phase A was 0.05 mol·L⁻¹ ammonium acetate solution-methanol(83∶17), mobile phase B was acetonitrile. The flow rate was 0.5 mL·min⁻¹ with gradient elution. The detection wavelength was 247 nm, the column temperature was 55 ℃, and the injection volume was 5 μL.

RESULTS Gefitinib and the impurities were separated well. The linear relationship between peak area and the concentration range of gefitinib and 14 known impurities(r>0.9994) were good enough. The limits of quantitation were 0.06–0.35 μg·mL⁻¹ and the limits of detection were 0.02–0.12 μg·mL⁻¹. The average recoveries of impurities 1–14 were 98.0%–102.0% and the correction factors were 0.47–3.65, respectively. The results of 146 batches gefitinib tablets from 9 different companies showed that the content of single impurity was less than 0.1%, and the total content of impurities was less than 0.2%. The overall quality of this product was good. The result of cluster analysis showed that impurity 4 could be considered as a key quality control impurity for the production and storage of gefitinib tablets, and impurities 8, 9, 11, 12, 13 and 14 could be considered as key quality control impurities of gefitinib raw material. Production enterprises could optimize the production process and screen high-quality APIs by monitoring the above impurities to improve product quality.

CONCLUSION This method is specific, simple and accurate, which can be used for the quality control of related substances in gefitinib tablets. The key quality control impurities established by cluster analysis can provide data support for controlling and evaluating the quality of gefitinib tablets.