Abstract: OBJECTIVE To improve the quality and provide technological support for reducing the impurity content of Compound Captopril tablet, the source and structure determination of the unknown-impurity is studied. METHODS A Kromasil Phenyl column (250 mm×4.6 mm, 5 μm) was used. The wavelength of UV detector was 210 nm. HPLC gradient elution was used with water-phosphoric acid (550︰0.5) and methanol as mobile phase to find the source and determine the content of the unknown impurity in Compound Captopril tablets. The structure of the unknown impurity was identified by LC-MS. RESULTS The unknown impurity was elucidated as C₁₆H₂₃N₄O₇S₃Cl, which was the dipolymer of hydrochlorothiazide and captopril by heating, and was included in most of the domestic generic Compound Captopril tablet. CONCLUSION This study provides reference for the improvement of quality control and process optimization of Compound Captopril tablet.