Objective: To investigate the related substances in ozagrel sodium for injection sampled in the market. Methods: An HPLC method for the evaluation of related substances in ozagrel sodium for injection was established. The chromatography was performed on Inertsil ODS C18 column with 0.01 mol·L-1 ammonium acetate buffer-methanol (80∶20) as mobile phase A and methanol as mobile phase B. The detection wavelength was set at 272 nm at the flow rate of 1.0 mL·min-1, and the sample volume was 20 μL. Forty-six batches of sodium ozagrel for injection were evaluated using the established method. Impurities with content >0.1% were scanned by Q-TOF high resolution mass spectrometry in ESI+ mode. Results: The detection limit of the proposed method was 0.010 μg·mL-1, and the destructive test results showed that ozagrel was well separated from impurities under this condition. It was found that the total amount of impurities in all samples was less than 1.0%, and the single maximum impurity (impurity I) with the content of 0.16%-0.23% was detected in 5 samples, and the total amount of impurities in these 5 samples reached 0.61%-0.69%. The single maximum impurity of each sample had no obvious change before and after the accelerated test, and the difference value of total impurity was <0.06%. The combined use of 0.9% sodium chloride injection and 5% glucose injection had no effect on the level of related substances. Impurity Ⅰ was inferred to be (E)-4-(1-imidazolmethyl) methyl cinnamate synthesized from ozgrel raw material by high resolution mass spectrometry combined with production process literature. Conclusion: The related substances in sodium ozagrel for injection in the market are in line with the existing quality standards of this variety in China. However, it is found that some impurities in the existing quality standards are not effectively monitored. The method developed in this article can effectively monitor the impurities of sodium ozagrel for injection and obtain comprehensive impurity information. The method can be further applied to product quality control of ozagrel raw materials and other ozagrel preparations.
YE Xiao-xia, JIANG Wen-ming, ZHANG Xue, CAO Wen, JIN Wei, LE Jian
. Study on the related substances of ozagrel sodium for injection[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(7)
: 1238
-1244
.
DOI: 10.16155/j.0254-1793.2023.07.18
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