OBJECTIVE: To prepare Pramipexole dihydrochloride sustained-release pellets capsules and to establish a method for the determination of related substances. METHODS: Drug loaded core was prepared by fluid bed air suspension coating method, and pramipexole dihydrochloride pellets were prepared using Surelease® as coating materials and put into capsules. HPLC method was used to determine related substance in sustained-release pellets; the determination was performed on Capcell PAK MG-Ⅱ C18 column (150 mm×4.6 mm, 5 μm) with mobile phase A consisted of ammonium formate buffer solution (pH 5.0) and mobile phase B consisted of methanol for gradient elution at flow rate of 1.0 ml/min; diode array detector was used with detection wavelength of 240, 262, 326 nm and injection volume of 80 μl. RESULTS: Pramipexole dihydrochloride and 7 kinds of related substances were separated by the established HPLC conditions. The blank excipient did not interfere with the assay of the related substances. The linear ranges of 7 related substances were 0.2-2 μg/ml (r>0.999 0); the limit of detection ranged 0.5-1.8 ng, and the limit of quantitation ranged 1.7-5.9 ng; average recovery ranged 98.93%-102.0% (RSD were 1.90%-0.24%,n=9). RSD of precision and stability test were all lower than 1.0% (n=5). Only one related substance was found in prepared Pramipexole dihydrochloride pellets capsules. CONCLUSIONS: Pramipexole dihydrochloride pellets capsules are prepared successfully. Established HPLC method can be used for the determination of its related substances.