Determination of Related Substances of Quetiapine Fumarate Tablet and Identification of Oxidative Degradation Products
Objective:To establish a High-performance Liquid Chromatography(HPLC)method for the determination of related substances in quetiapine fumarate tablets.The impurities were identified by high resolution mass spectrometry(HRMS).Methods:Effects of different concentration,pH,column temperature on the separation for target compounds were compared.The target compounds were separated on an Agilent 5TC-C18(2)column(250 mm×4.6 mm,5 µm)by gradient elution with 15 mmol/L ammonium acetate and acetonitrile as the mobile phases.The effects of different concentrations,pH,and column temperature on separation efficiency were investigated.The mass spectrometer was operated in HESI ion source,positive detection mode.Fragmentation analysis was used Mass Frontier 8.0 and Compound Discoverer 3.3 to verify and analyze the impurities.The structures of the impurities were speculated.Combined with the standards and the literature report,to verify the accuracy of the inferred results.Results:Under the optimized conditions,related substances were completely separated from the major constituents.Quetiapine showed good linear relationships within the range of 0.01～1.5 μg/mL(r=0.9999),the limit of detection(LOD)was 0.005 μg/mL,and the limit of quantification(LOQ)was 0.016 μg/mL.According to the HRMS results,six impurities were speculated.Conclusion:This method can effectively separate quetiapine and its impurities,and has the characteristics of simple,high sensitivity,specificity,accuracy,durability and feasibility.It provides reference for the determination of related substances in Quetiapine fumarate tablets.
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