High-Speed Analysis of Pramipexole

Significance of the Topic

Pramipexole is a dopamine agonist widely used in the management of Parkinson’s disease. Accurate and rapid analysis of pramipexole and its related impurities is critical for ensuring product safety and regulatory compliance in pharmaceutical quality control. Advances in chromatographic methods, particularly UHPLC, offer opportunities for faster, more efficient impurity testing without compromising performance.

Objectives and Overview of the Study

This study compared a United States Pharmacopeia (USP)–compliant reversed-phase HPLC method with an optimized UHPLC protocol using Shim-pack GIST C18 columns. The aim was to shorten run time and reduce solvent usage while maintaining or improving separation of pramipexole and its known impurity (Compound A).

Methodology

Both methods employed a mobile phase A consisting of 67 mmol/L potassium phosphate buffer (pH 3.0) with 21 mmol/L sodium 1-octanesulfonate and mobile phase B as a 1:1 mixture of buffer and acetonitrile. A gradient elution was applied:

• USP Method: 40 % B at 0 min to 80 % B at 15 min, return to 40 % B by 15.1 min, total runtime 20 min
• UHPLC Method: 40 % B at 0 min to 80 % B at 2.00 min, return to 40 % B by 2.01 min, total runtime 3.5 min

Detection was performed at 264 nm UV. Sample injections were 5 μL for the USP method and 1 μL for UHPLC.

Instrumentation Used

• Nexera-i MT system (Shimadzu Corporation)
• Shim-pack VP-ODS column, 150 × 4.6 mm I.D., 5 µm (USP method)
• Shim-pack GIST C18 column, 50 × 2.1 mm I.D., 2 µm (UHPLC method)
• UV detector at 264 nm

Main Results and Discussion

• The USP method achieved baseline separation of pramipexole and its impurity within a 20-minute run time with acceptable resolution.
• The UHPLC approach compressed the gradient into 2 minutes, delivering equivalent resolution and sharper peaks, reducing total analysis time to 3.5 minutes.
• Solvent consumption was cut by nearly 50 % due to the lower flow rate and shorter run time, while sample throughput increased more than fivefold.

Benefits and Practical Applications

• High-throughput capability supports routine QC testing in pharmaceutical manufacturing environments.
• Reduced solvent usage aligns with green chemistry initiatives and lowers operating costs.
• Maintains compliance with USP impurity guidelines while enhancing laboratory efficiency.

Future Trends and Opportunities

Emerging ultrahigh-pressure and core-shell column technologies, combined with mass spectrometry detection, will facilitate even faster and more sensitive impurity profiling. Integration of automated sample preparation and real-time data analytics is expected to enhance reproducibility and enable continuous monitoring within manufacturing workflows.

Conclusion

Transitioning to a UHPLC method using Shim-pack GIST C18 columns provides a rapid, reliable, and cost-effective solution for the analysis of pramipexole dihydrochloride and its impurities. The method meets USP requirements and delivers substantial improvements in analysis speed and solvent economy.

References

• Shimadzu Corporation. Application News L524: High-Speed Analysis of Pramipexole Dihydrochloride using Shim-pack GIST C18. First Edition, Dec. 2021.