Objective:To identify the related substances of eicosapentaenoic acid ethyl ester in soft capsules by liquid chromatography tandem mass spectrometry (LC-MS). Methods: The chromatographic separation was carried out on a Thermo AcclaimTM 120 C18 column (250 mm×4.6 mm, 5 μm) with linear gradient elution by acetonitrile-ammonium formate solution as the mobile phases, the flow rate was 1.0 mL·min-1, the detection wavelength was 190 nm, and the injection volume was 50 μL. The accurate mass and elemental composition of the parent ions and their product ions of the related substances were determined by atmospheric pressure chemical ionization combined with a high-resolution quadrupole time-of-flight mass spectrometry (APCI-Q TOF/MS). Some structures of the related substances were further confirmed by reference substances. Results: The established LC-Q TOF/MS method was suitable for ethyl polyenoate related substances determination. 20 major rela-ted substances were detected and identified in ethyl eicosapentaenoate preparation and its forced degradation pro-ducts. The forced degradation tests showed that the preparation of ethyl eicosapentaenoate was sensitive to strong acid, alkali, dry heat, intense light and humid environment, and the cis-double bond in the structure might be isomerized to generate corresponding cis and trans isomers impurities. Conclusion: The identification results of related substances in ethyl eicosapentaenoate soft capsules can provide good reference for the production processes optimization, stability evaluation and quality control of the product.
LIN Ying-yu, PAN Jing-ru, SONG Min, LU Yu-ting, HANG Tai-jun
. Identification of the related substances of eicosapentaenoic acid ethyl ester soft capsules by LC-Q TOF/MS[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(10)
: 1774
-1783
.
DOI: 10.16155/j.0254-1793.2023.10.16
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