A rapid ibuprofen USP assay method

Significance of the Topic

Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drugs. Reliable, high-throughput assays are critical in pharmaceutical development, quality control, and generic manufacturing. Modernizing United States Pharmacopeia (USP) methods reduces analysis time, solvent consumption, and operational costs while preserving regulatory compliance.

Objectives and Study Overview

This work aimed to enhance the USP monograph assay for ibuprofen by applying modern solid core column technologies and advanced UHPLC instrumentation. The main goals were to dramatically increase sample throughput, minimize solvent waste, and adhere to USP-NF Chapter <621> quality criteria.

Methodology and Instrumentation

The optimization process followed USP guidelines for isocratic methods with adjustments in particle size, column length, and flow rate. Key steps included:

• Evaluating Hypersil GOLD (5 µm, 150×4.0 mm) versus Accucore XL C18 (4 µm, 150×4.6 mm) and Accucore C18 (2.6 µm, 100×4.6 mm and 50×2.1 mm).
• Scaling flow rates based on column diameter (F ∝ d_c²/d_p).
• Simplifying the mobile phase to 0.1% formic acid in water and acetonitrile.
• Raising column temperature from 30 °C to 50 °C.

Used Instrumentation:

• Vanquish Flex Quaternary UHPLC system with SmartInject™ and LightPipe™ flow cell DAD
• Accucore C18 solid core columns (150×4.6 mm, 100×4.6 mm, 100×2.1 mm, 50×2.1 mm)
• Chromeleon™ 7.2 SR4 software

Main Results and Discussion

Transitioning from a 5 µm, 150×4.0 mm column at 2.0 mL/min to a 2.6 µm, 100×2.1 mm column at 0.417 mL/min reduced run time from 20 to 7 minutes and solvent use by eight-fold. Further shortening to a 50×2.1 mm column at 1.0 mL/min and 50 °C achieved a 4-minute assay with 4 mL mobile phase use. Throughout, resolution between ibuprofen and the impurity valerophenone remained above the USP threshold of 2.0, and plate counts stayed within acceptable limits. A 24-injection repeatability study confirmed robust retention time and area precision.

Benefits and Practical Applications

• Five-fold increase in sample throughput
• Ten-fold reduction in cost per sample via decreased solvent consumption and waste volume
• Maintenance of USP quality acceptance criteria (resolution and repeatability)
• Simplified mobile phase preparation enhances routine QC workflows
• Lower environmental impact through reduced waste generation

Future Trends and Opportunities

Solid core UHPLC architectures and intelligent UHPLC systems are set to revolutionize pharmacopeial assays beyond ibuprofen, enabling faster stability and dissolution testing. Integration with mass spectrometry, adoption of greener solvents, and automated data processing will further boost laboratory efficiency, sustainability, and data confidence.

Conclusion

The modernized ibuprofen USP assay cut analysis time from 20 to 4 minutes and reduced solvent usage from 40 mL to 4 mL while preserving critical performance metrics. This approach demonstrates a scalable pathway for updating legacy pharmacopeial methods to meet contemporary laboratory demands.

References

• Accucore HPLC columns technical guide, Thermo Fisher Scientific