Objective: To establish a method for the determination of unknown impurities in benproperine and identify the structure of two unknown impurities.Methods: An Inertsil ODS-3(4.6 μm, 2.1 mm×150 mm) column was adopted for the study.The mobile phase was methanol-0.01 mol·L-1 sodium acetate buffer solution (Take ammonium acetate 0.77 g, dissolved by 800 mL of water, adjust the pH to 3.3 by acetic acid, diluted with water to 1 000 mL) (65:35).The flow rate was 0.25 mL·min-1, the detection wavelength was 270 nm.Two impurities were analyzed by HPLC-MS/MS, and was then separated and purified by preparative HPLC, and the structure were confirmed by nuclear magnetic resonance(1H-NMR, 13C-NMR, HMBC, HSQC, DEPT135, H-H COSY).Results: Two unknown impurities were 1-[2-(2-benzoylphenoxy)-1-methylethyl] piperidine and 1-[2-(2-benzyl-6-chlorophenoxy) -1-methylethyl] piperidine.Conclusion: The established method can provide a comprehensive reference for quality control of benproperine.
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