Objective: To establish an HPLC method for the determination of related substances in pramipexole dihydrochloride sustained-release tablets. Methods: Two chromatographic methods were used to determine the related substances. Condition 1: HC-5 C18 (250 mm×4.6 mm, 5 μm) column was used, with ammonium formate buffer (pH 5.0)-methanol (99 ∶ 1) as mobile phase A and ammonium formate buffer (pH 5.0)-methanol (44 ∶ 56) as mobile phase B, the gradient elution was performedat a flow rate of 1.0 mL · min-1,the detection wavelengths were 240, 262 and 326 nm respectively, the column temperature was 40 ℃, and the injection volume was 100 μL. Condition 2: Inertsil ODS-3 (150 mm×3.0 mm, 3 μm) column was used, with phosphate buffer (containing 0.5% sodium octane sulfonate, pH 3.0)-acetonitrile (90 ∶ 10) as mobile phase A, and phosphate buffer (containing 0.5% sodium octane sulfonate, pH 3.0)-acetonitrile (72 ∶ 28) as mobile phase B, the gradient elution was performedat a flow rate of 0.7 mL · min-1, the detection wavelengths were 240, 262 and 326 nm respectively, the column temperature was 40 ℃, and the injection volume was 100 μL. Results: 12 known impurities were separated and detected under condition 1, while other known impurities were separated under condition 2. An excellent linear relationship was established between pramipexole dihydrochloride and its 14 impurities, and the recovery rate of each impurity (n=9) was determined to be 95.0%-105.0%. The minimum detection limit was found to be 2.0-13.0 ng · mL-1. The forced degradation experiment further confirmed that the degradation products under different conditions could be effectively indicated by this method. The results of testing four batches of pramipexole dihydrochloride sustained-release tablets showed that. Under condition 1, impurity 1 was present at 0.07%-0.09%, impurity 2 at 0%-0.01%, and impurity 11 at 0.04%, with total impurities at 0.11%-0.14%. Under condition 2, impurity 2 was found at 0.01%-0.02%, Impurity 6 at 0%-0.06%, impurity 12 at 0%-0.02%, and unknown total impurities at 0%-0.09%, with total impurities at 0.01%-0.16%. Conclusion: The HPLC method established in this study not only optimizes the sample preparation process, but also significantly improves the accuracy and reliability of detection, with good reproducibility, and making it suitable for the quality control of pramipexole dihydrochloride sustained-release tablets.
YE Jun
,
SONG Lei
. Determination of related substances in pramipexole dihydrochloride sustained-release tablets by HPLC[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(7)
: 1233
-1243
.
DOI: 10.16155/j.0254-1793.2025-0002
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