Objective To establish HPLC analysis methods for controlling the related substances and its enantiomer in the active pharmaceutical ingredient of rotigotine.

Methods The HPLC chromatographic conditions for related substances were as follows: the separation was performed on a Waters Sunfire C₁₈ column (150 mm × 4.6 mm, 3.5 μm) with a mobile phase consisting of potassium dihydrogen phosphate buffer (pH 6.55±0.05, mobile phase A), acetonitrile (mobile phase B), and methanol (mobile phase C) with gradient elution, the detection wavelength was 220 nm, the flow rate was 1.0 mL/min, the column temperature was 40 ℃, and the injection volume was 10 μL. The HPLC chromatographic conditions for enantiomer were as follows: the separation was performed on a CHIRALPAK IB N-5 chiral column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of n-hexane-diluent (anhydrous ethanol isopropanol=95∶5)-diethylamine (97∶3∶0.1), the detection wavelength was 225 nm, the flow rate was 0.8 mL/min, the column temperature was 35 ℃, and the injection volume was 5 μL.

Results In the determination of related substances, rotigotine was well separated from its known impurities. The linearity of all components was satisfactory within the investigated concentration ranges (r ≥ 0.9970). The average recoveries at three spiked levels (limit of quantitation, 100% limit, 150% limit) ranged from 95.7% to 104.5%, with RSDs ≤ 4.80% (n = 9). In the determination of the enantiomer, impurity A exhibited a good linear relationship within the concentration range of 1.4-8.8 μg/mL (r = 1.0000). The average recoveries at three spiked levels (limit of quantitation, 100% limit, 150% limit) were 124.0%, 101.1%, and 114.2%, and RSDs were 4.69%, 1.88% and 0.78% (n = 9), respectively.

Conclusion The method is specific, sensitive, accurate, and robust, and can be applied for the quality control of related substances and the enantiomer in the active pharmaceutical ingredient of rotigotine.

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