Objective: To establish a methodology for the control of related substances in revefenacin nebulizer solution. Methods: 2D LC-HRMS was employed to confirm the structure of the degraded impurities, and specific impurities were selected based on the possible degradation pathways. An InfinityLab Poroshell 120 C18(250 mm× 4.6 mm, 4 μm) column was utilized, with 0.02 mol · L-1 potassium dihydrogen phosphate solution (pH was adjusted to 7.5 by 2 mol · L-1 potassium hydroxide solution)-methanol (93 ∶ 7) serving as mobile phase A. Acetonitrile was employed as mobile phase B, with gradient elution at a flow rate of 1.0 mL · min-1. The detection wavelength was set at 230 nm and the column temperature was maintained at 35 ℃. The impurities were quantitatively analyzed by the principal component self-control method with correction factor. Results: The main degradation pathways were oxidation reaction and hydrolysis reaction, and the main degradation products were impurity A, impurity B and impurity C. Under the proposed chromatographic conditions, the principal component peak of revefenacin was completely separated from each impurity peak, and each excipient component did not interfere with the determination of the principal component and related substances. The relative correction factors of impurity A, impurity B and impurity C were 1.27, 1.08 and 1.06, respectively. No impurities exceeding the reported limit were detected in multiple batches of samples on 0 d, and the content of impurity B was 0.31%, the maximum unknown impurity content was 0.15%, and the total impurity was 1.06% after 30 d in high temperature. Conclusion: The method exhibits strong specificity and good repeatability, and can be applied on the detection of related substances in revefenacin nebulizer solution.
TANG Yu-qi
,
SHEN Meng-meng
,
LIU Zi-qing
,
XIAO Chao-qiang
,
WANG Xu
. Research on the inspection method for related substances in the revefenacin nebulizer solution*[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(4)
: 686
-695
.
DOI: 10.16155/j.0254-1793.2024-0409
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