Objective: To establish a detection method for the seven related substances (related substances 1-7) of ixabepilone API by HPLC and provide a method basis for the quality control of ixabepilone. Methods: Welch XB-C18 column(250 mm×4.6 mm,3 μm) was adopted, the mobile phase consisted of acetonitrile-0.04 mol·L-1 ammonium acetate aqueous solution with gradient elution. The flow rate was 1.0 mL·min-1, the column temperature was 25 ℃, the detection wavelength was 249 nm and the injection volume was 10 μL. Results: The chromatographic peaks of ixabepilone and its seven related substances were well separated. A good linear relationship was shown between the mass concentration of 1-7 related substances of ixabepilone and the corresponding peak area within the concentration range of 0.05-2 μg·mL-1(r≥0.999 5). The limits of quantification were 0.025, 0.033, 0.043, 0.036, 0.036, 0.108 and 0.032 μg·mL-1, respectively, and the average recoveries (n=9) were 98.5%, 98.3%, 101.2%, 100.3%, 97.6%, 101.0% and 98.6% with RSDs of 2.3%, 2.8%, 3.3%, 2.1%, 2.6%, 5.7% and 3.6%, respectively. The detection results of 3 batches of ixabepilone samples showed that the contents of known impurities and other maximum single impuritie were less than 0.083%, and the total content of impurities was less than 0.256%. Conclusion: The detection method has demonstrated strong specificity and high accuracy, it could be used for the related substances of ixabepilone API, and fill the blank of the detection method of related substances of ixabepilone at home and abroad.
FU Yao, LIU Song-xia, FAN Cai-xia, PENG Ji-ming, JIN Dun-qing, HOU Jun
. Detection of related substances of ixabepilone by HPLC*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(10)
: 1801
-1807
.
DOI: 10.16155/j.0254-1793.2022.10.13
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