High-Speed Analysis of Pramipexole following the Draft Guidance of International Harmonization of Pharmacopoeias

Significance of the Topic

The adoption of ultra-high performance liquid chromatography (UHPLC) has become essential in pharmaceutical analysis to boost throughput and productivity. With ongoing harmonization efforts among USP, EP and JP for allowable ranges in gradient elution, high-speed methods are expected to gain official acceptance. This drives the need for reliable method transfer and robust workflows.

Objectives and Study Overview

This work aims to demonstrate a high-speed analysis of pramipexole dihydrochloride analogs based on the draft international harmonization guidelines. The study evaluates method conversion from the USP monograph HPLC procedure to a UHPLC format using Shimadzu’s Nexera-i MT system.

Instrumentation

• UHPLC system: Shimadzu Nexera-i MT
• Software: LabSolutions with dedicated Method Transfer tool
• Analytical Columns:
  
  • HPLC: Shim-pack VP-ODS, 150 × 4.6 mm, 5 µm
  • UHPLC: Shim-pack GIST C18, 50 × 2.1 mm, 2 µm
• Detector: UV at 264 nm

Methodology and Analytical Conditions

Gradient elution conditions were recalculated to maintain equivalent gradient volume per column volume using established scaling equations. Flow rates and gradient times were adjusted according to column dimensions and particle sizes. The injection volume was scaled relative to column cross-sectional area. Both methods used a phosphate buffer with 1-octanesulfonic acid and an organic modifier for the mobile phase.

Main Results and Discussion

• Analysis time was reduced from 20 min to 3.5 min without compromising separation quality.
• System suitability tests showed comparable performance with resolution >10, tailing factor <1.1 and RSD <0.3% for both methods.
• The Method Transfer tool facilitated error-free parameter adjustment and direct method file generation.

Benefits and Practical Applications

The high-speed UHPLC approach offers significant solvent and time savings, enabling higher sample throughput. Automated method transfer reduces manual work and transcription errors, enhancing operational efficiency in quality control laboratories.

Future Trends and Opportunities

With impending adoption of harmonized gradient guidelines, tools for seamless method transfer will become integral to analytical labs. Future developments may include integration with digital laboratory systems, AI-driven method optimization, and expansion to a broader range of assays.

Conclusion

The study confirms that pramipexole analog analysis can be effectively migrated to a UHPLC format, achieving rapid and robust separations in alignment with international guidelines. Shimadzu’s method transfer capabilities are shown to streamline this process.

References

• International Harmonization (Stage 4), Pharmaceuticals and Medical Devices Agency.
• USP Pharmacopoeia 40:5795 Pramipexole Dihydrochloride.