Objective: To study the molecular structure and formation route of impurity II (accurate molecular weight 286.081 44) in pemirolast potassium tablets, and to provide suggestion for improvement of preparation formulation. Methods: The compatibility study between pemirolast potassium and carboxymethyl starch sodium (CMS) was performed by using HPLC to determine the impurity content and UPLC-HRMS to characterize the structure of the impurity. HPLC was applied with a Shimadzu Intersil ODS-SP column (150 mm×4.6 mm, 5 μm) and eluted with aqueous solution of 0.1% trifluoroacetic acid-acetonitrile (84∶16) under the condition of detection wavelength 257 nm and column temperature 40 ℃. UPLC was applied with a Waters ACQUITY HSS T3 column (100 mm×2.1 mm, 1.7 μm) and eluted with water-methanol-glacial acetic acid (90∶10∶0.2). MS was applied with HESI source and positive/negative ion modes. Fragment analysis was carried out by MsFrontier 7.0 software. Results: Through compatibility test and MS analysis, it was clarified that the solid-solid chemical reaction between API and the residual chloroacetic acid in the excipient carboxymethyl starch sodium was the cause of the formation of impurity Ⅱ in the tablets. Conclusion: The selection of CMS as an excipient in the prescription of pemirolast potassium tablets by some generic pharmaceutical companies probably causes the risk of formation of impurity Ⅱ. It is recommended that the manufacturers optimize the tablet prescriptions and reduce the safety risks caused by the drug-excipient incompatibility.
CHENG Jie, WU Xiao-ying, LI Xian-qing, TANG Xiu-xiu, LI Lei, XIE Zi-li
. Formation and analysis of the impurity derived from drug-excipient incompatibility in pemirolast potassium tablets*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(12)
: 2107
-2114
.
DOI: 10.16155/j.0254-1793.2021.12.09
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