Objective: To establish an HPLC method for determination of the impurity profile in furosemide and its injection. At the same time,applying this method to detect and analyze products from many domestic and foreign enterprises,to evaluate the status quo of impurity control in API and injection,and the correlation of major degraded impurities in injection with prescription and packaging materials. Methods: A YMC Hydrosphere C18 column(250 mm×4.6 mm,3 μm)was used,and the mobile phase was 0.05% TFA solution (pH 2.23)-methanol-acetonitrile at the flow rate of 1.0 mL·min-1,gradient elution. Detection wavelength was set at 238 nm and 277 nm and column temperature was 30 ℃. Impurity reference was used for localization and the relative retention time of each impurity was calculated. The known impurities were calculated using the principal component self-control method with correction factor,the unknown impurities were determined by principal component without correction factor. Results: The method for the determination of 11 kinds of known impurities, the potential genotoxic impurity in furosemide, its injection was established,the separation degree of all impurities met the requirements,and the sources of the impurities were identified by forced degradation test. The detected quantity of degraded impurity C and degraded impurity G in the injections produced by 2 to 3 companies exceeded the identification limit in ICH by 0.2%, the amount of potential genotoxic impurity furfural detected in the injection of 5 enterprises was much higher than that of the reference preparation,other impurities were the same as the reference preparation. Conclusion: The established HPLC method can be used for rapid detection and analysis of impurities in furosemide and its injection. The impurity control level of injection produced by only 2 domestic enterprises is basically consistent with the reference preparation,others need to optimize prescription and packaging materials. This study can provide reference for improving the safety of furosemide injection and evaluating the quality consistency of generic drugs.
WANG Xiao-jing, ZHANG Xiao-ming, KE Jing, WANG Wen-li, ZHANG Xiao-yan, SUN Ying, GUO Zhao-hui
. Impurity profile study of furosemide and its injection*[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(8)
: 1443
-1453
.
DOI: 10.16155/j.0254-1793.2023-0535
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