Preparative Purification of Ibuprofen and Its Related Substance (Shim-pack UFPLC)

Importance of the Topic

Ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs). Its high demand and strict quality requirements call for efficient preparative and analytical workflows to isolate the active pharmaceutical ingredient (API) and monitor related impurities. The development of reliable purification methods enhances drug safety, reduces downstream processing costs, and supports regulatory compliance.

Study Objectives and Overview

This application note demonstrates a two-step approach: preparative purification of ibuprofen and its structurally related impurities using a Shimadzu Nexera UFPLC system, followed by analytical verification of purity on a Nexera XR platform. The study aims to achieve high-purity fractions with reproducible separation performance and simplified method transfer between scales.

Methodology and Instrumentation

Analytical Purity Verification

• System: Nexera XR
• Column: Shim-pack Scepter C18-120 (150 mm × 4.6 mm I.D., 5 µm)
• Mobile phase A: 1 % (w/v) chloroacetic acid in water, pH 3; B: acetonitrile; A/B = 40/60 (v/v)
• Flow rate: 0.8 mL/min; Column temp.: 30 °C; Detection: 230 nm; Injection: 10 µL

Preparative Purification

• System: Nexera UFPLC
• Column: Shim-pack Scepter C18-120 (150 mm × 20 mm I.D., 5 µm)
• Mobile phase A: same as analytical; B: acetonitrile; A/B = 40/60 (v/v)
• Flow rate: 20 mL/min; Detection: 230 nm; Injection: 2000 µL
• Rinsing: Shim-pack UFPLC 20×30 cartridge, solvents acetonitrile/water (2/98), 0.2 % formic acid, water; gradient flow program applied
• Elution of collected fractions: acetonitrile at 9 mL/min with 230 nm detection

Key Results and Discussion

Chromatograms obtained on the preparative system show baseline separation of ibuprofen from valerophenone and 4-isobutyl-acetophenone impurities. Fractions collected under the defined gradient exhibited high recovery and minimal cross-contamination. Analytical verification confirmed that purified ibuprofen met stringent pharmacopeial purity criteria, demonstrating method robustness and reproducibility.

Benefits and Practical Applications

The described workflow enables:

• Scalable purification of ibuprofen for pilot and production scales
• Rapid method development using identical stationary phases on analytical and preparative systems
• Reduced solvent usage and simplified system rinse procedures
• Enhanced quality control through direct method transfer

Future Trends and Potential Applications

Emerging opportunities include integrating mass spectrometric detection for real-time impurity profiling, automating fraction collection with feedback control, and extending the approach to other NSAIDs and complex small molecules. Advances in column chemistry and micro-flow ultrafast LC are expected to further accelerate preparative workflows.

Conclusion

This study validates a robust LC-based platform for preparative purification and analytical confirmation of ibuprofen. The consistent use of C18-120 stationary phase across scales facilitates method transfer, delivering high-purity API fractions with operational efficiency. The approach supports quality assurance in pharmaceutical manufacturing.

References

• Shimadzu Application News an_01-00464 (JP, ENG), First Edition Aug. 2023