Rapid Separation of Ibuprofen, Ibuprofen- Related Compound C, and Valerophenone Using Advanced UHPLC and Sub-2 μm Solid Core Column Technologies

Significance of the Topic

Ibuprofen is one of the most commonly used NSAIDs, and rapid, reliable analysis of its purity and related impurities is essential for pharmaceutical quality control. Advances in column and system technology enable faster analysis times while maintaining or improving chromatographic performance, increasing laboratory throughput and reducing solvent consumption.

Study Objectives and Overview

This study compares a conventional 4 µm core–shell C18 column with a modern 1.5 µm Accucore Vanquish C18+ column on a Vanquish UHPLC system. The goal is to demonstrate how the high-pressure UHPLC platform and sub-2 µm solid-core particles can shorten analysis time for the separation of ibuprofen, ibuprofen-related compound C, and valerophenone, while meeting USP criteria for resolution, peak shape, and retention time reproducibility.

Applied Methodology and Instrumentation

• Mobile phase: water with 1 % chloroacetic acid (pH 3) and acetonitrile (40:60 v/v).
• Comparison methods:
  • 4 µm column: Accucore XL C18, 150 × 4.6 mm, flow rate 2 mL/min, injection 5 µL.
  • 1.5 µm column: Accucore Vanquish C18+, 100 × 2.1 mm, flow rate 0.65 mL/min, injection 1 µL.
• Column temperature: 30 °C; detection by UV at 254 nm (0.1 s rise time, 50 Hz, 8 nm slit width).
• Sample preparation: ibuprofen (0.35 mg/mL) and valerophenone (12 mg/mL) spiked with 0.1 % ibuprofen-related compound C (0.012 mg/mL).

Instrumentation

Vanquish UHPLC system comprising a system base, binary pump H (up to 1500 bar), split sampler HT, column compartment, diode array detector HL, and Viper low-dispersion connections. Data acquisition was performed with Chromeleon 7.2 SR2.

Main Results and Discussion

Switching from a 4 µm, 150 × 4.6 mm column to a 1.5 µm, 100 × 2.1 mm column reduced the total run time from 2.5 minutes to 1.5 minutes. The 1.5 µm column met USP resolution requirements (>2.0 between ibuprofen and valerophenone), exhibited symmetrical peaks (asymmetry <1.5), and demonstrated excellent retention time reproducibility (%RSD ≤0.04). Chromatograms showed clear separation of ibuprofen, valerophenone, and the related impurity within the shortened runtime.

Benefits and Practical Applications

• Increased sample throughput and laboratory efficiency.
• Reduced solvent use and operating costs.
• Maintained compliance with USP monographs for quality control in pharmaceutical analysis.
• Improved chromatographic resolution and peak shape for accurate quantitation of impurities.

Future Trends and Possibilities

The combination of sub-2 µm core–shell columns and high-pressure UHPLC systems opens opportunities for further miniaturization, coupling with mass spectrometry for enhanced sensitivity, and automation of method development. Such advances will extend rapid, high-resolution analysis to a broader range of compounds in drug development, metabolomics, and environmental testing.

Conclusion

Adopting Accucore Vanquish C18+ 1.5 µm columns on a Vanquish UHPLC system enables up to 40 % faster separations of ibuprofen and related impurities while maintaining strict USP quality criteria. This approach supports high-throughput pharmaceutical QC with optimized efficiency and performance.

References

No external references were cited in the original document.