Adapt the USP Naproxen Tablet Method for Agilent InfinityLab Poroshell 120 4 μm Columns

Significance of the Topic

Naproxen is a widely used NSAID requiring rigorous QC/QA analysis in pharmaceutical labs to ensure dosage accuracy and regulatory compliance.

Objectives and Study Overview

This study adapts the USP monograph for naproxen tablets to modern superficially porous column technology, aiming to reduce solvent consumption and improve throughput without altering core method parameters beyond USP <621> allowable adjustments.

Methodology and Instrumentation

• Sample Preparation: Tablets dissolved in acetonitrile:water (90:10) with butyrophenone as internal standard; Naproxen RS at ~25 µg/mL.
• Chromatographic Conditions: Mobile phase acetonitrile:water:glacial acetic acid (50:49:1); flow rate 1.2 mL/min; injection volume 20 µL (150 mm columns) or 13.34 µL (100 mm column); column temperature 25 °C; detection at 254 nm.

Instrumentation

• Agilent 1260 Infinity Binary Pump SL (G1312B)
• Agilent 1260 Infinity Diode Array Detector SL (G4212)
• Agilent 1260 Infinity Automatic Liquid Sampler SL (G1376C)
• Agilent 1260 Infinity Thermostatted Column Compartment SL (G1316B)

Main Results and Discussion

The Agilent InfinityLab Poroshell 120 EC-C18 4 µm, 4.6 × 150 mm column delivered ~19,054 theoretical plates (79% increase) versus 10,639 plates on the 5 µm USP reference column, at similar run times. A 4.6 × 100 mm variant provided 13,186 plates with a 33% shorter run time. Backpressure remained under 200 bar, compatible with conventional HPLC systems. Throughput rose from ~6–7 analyses per hour to higher rates under allowable USP adjustments.

Benefits and Practical Applications

• Significantly higher chromatographic efficiency and resolution.
• Reduced analysis time and solvent consumption.
• Improved laboratory productivity and cost savings.
• Seamless integration on existing HPLC instruments.

Future Trends and Opportunities

Adoption of superficially porous column technologies in compendial methods is expected to expand, enabling faster assays and lower solvent use. Further method optimization within USP <621> guidelines can support high-throughput QC workflows and transitioning to fast-LC formats.

Conclusion

The Agilent InfinityLab Poroshell 120 EC-C18 4 µm columns can be implemented as drop-in replacements for USP naproxen tablet assays, delivering enhanced efficiency, reduced run times, and cost-effective analyses while maintaining compendial compliance.

References

• USP Naproxen Tablet Method, United States Pharmacopeia 31 NF 26; 2008.
• USP Method Validation Guidance <621>, USP 30 Supplement 2; 2013.
• USP Method Validation Guidance <621>, USP 30 Supplement 2; 2014.