Fast methods for the determination of ibuprofen in drug products

Significance of the Topic

Rapid and reliable quantification of active pharmaceutical ingredients is critical for quality control in drug manufacturing. Ibuprofen, one of the most widely used analgesics, is typically assayed by United States Pharmacopeia (USP) methods that rely on conventional HPLC and require lengthy run times, high solvent consumption, and elevated per-sample costs. Adopting modern UHPLC technology with optimized columns can drastically improve throughput while maintaining pharmacopeial acceptance criteria.

Study Objectives and Overview

This work evaluates the performance of a high-speed UHPLC method for ibuprofen in tablet formulations versus the official USP monograph procedure. The aim is to reduce analysis time, solvent usage, and cost without compromising critical parameters such as resolution, tailing, and relative retention time (RRT). Method development includes mobile phase screening, column dimension and particle size optimization, and validation of assay performance in real tablet samples.

Methodology and Instrumentation

The study employed a Thermo Scientific Vanquish Horizon UHPLC system controlled via Chromeleon CDS 7.2 or Waters Empower 3 with DII integration. Key experimental steps:

• Mobile phase screening in isocratic mode (25–50% acetonitrile with 0.1% phosphoric acid).
• Comparison of two methods: USP-compliant HPLC (250×4.6 mm, 5 μm column, 40:60 water/ACN + 0.4% chloroacetic acid, 8 min run) and fast UHPLC (50×2.1 mm, 2.6 μm core-shell column, 60% ACN + 0.4% chloroacetic acid, 0.5 min run).
• Sample preparation: tablet powder extraction in 60% ACN + 0.4% chloroacetic acid, centrifugation, and injection.
• Calibration: five standards from 1 to 10 mg/mL; internal standard valerophenone at fixed concentration.

Main Results and Discussion

Mobile phase screening demonstrated that at 50% acetonitrile the resolution between ibuprofen and valerophenone exceeded 4 with run times under 2 min and backpressure of only 230 bar. The optimized fast method delivered retention times of 0.26 min (ibuprofen) and 0.32 min (valerophenone), compared to 5.7 min and 7.4 min in the USP method. Resolution remained above the pharmacopeial minimum (>2.0), and tailing factors were 1.1 versus 1.2. Tablet assays showed recovery of 108% (fast) and 103% (USP), with RRT and area precision below 0.3% RSD. Ibuprofen content measured at 98% (fast method) and 99% (USP method) of label claim, both within the 90–110% requirement.

Benefits and Practical Applications

The fast UHPLC approach achieves:

• 94% reduction in analysis time.
• 97% decrease in solvent consumption.
• 69% lower cost per sample (assuming 1,000 injections).

These improvements facilitate high-throughput release testing in pharmaceutical QA/QC laboratories, minimize environmental impact, and leverage existing chromatographic infrastructure and data systems.

Future Trends and Opportunities

Further advancements may include adoption of sub-2 μm core-shell and fully porous particles under ultra-high pressures, integration of ultra-fast screening in multi-analyte pharmaceutical panels, and green solvent strategies. Coupling UHPLC with high-resolution MS and automated data workflows will enhance method robustness and expand applications in impurity profiling and stability studies.

Conclusion

The developed UHPLC method for ibuprofen quantification meets USP acceptance criteria while delivering a dramatic increase in analytical throughput and cost efficiency. Its implementation in routine quality control can streamline pharmaceutical testing and support sustainability goals.

Reference

1. United States Pharmacopeia. General Chapter <621> Chromatography. USP 40–NF 35, Rockville, MD, 2017.
2. United States Pharmacopeia. Ibuprofen Monograph. USP 40–NF 35, 2017, pp. 4555–4559.
3. Thermo Fisher Scientific. Application Note 21680: Rapid Ibuprofen USP Assay Method, 2016.
4. Thermo Fisher Scientific. Application Note 21183: Rapid Separation of Ibuprofen and Related Compounds Using UHPLC, 2015.
5. Kresge GA et al. Using Superficially Porous Particles and UHPLC in Pharmacopeial Modernization of Common Analgesics. Chromatographia, submitted 2018.
6. United States Pharmacopeia. S2: Chromatographic Columns and Packings. USP 40–NF 35.