Reductions in Cost and Time by Modernizing a USP Monograph Method from HPLC to UHPLC and UPLC Instrumentation and Columns

Importance of the Topic

Naproxen sodium is a widely used over-the-counter NSAID, and its consistent quality must be confirmed through reliable assays. Traditional USP monograph methods often rely on older HPLC setups that entail long run times and high solvent consumption. Modernizing these assays to UHPLC and UPLC platforms can deliver substantial improvements in throughput, cost efficiency, and environmental impact while adhering to USP <621> guidelines.

Study Objectives and Overview

This work aimed to migrate the USP assay for naproxen sodium tablets from conventional HPLC to UHPLC and UPLC systems. Goals included comparing assay performance, quantifying reductions in analysis time and mobile phase usage, and assessing column lifetime over 10 000 injections. Cost and time savings across the column lifespan were then estimated for each platform.

Methodology and Instrumentation

Sample Preparation:

• Five 220 mg tablets crushed, dissolved in 1 L of 85:15 water–acetonitrile (ACN) with 1% acetic acid.
• Filtered through 0.2 µm nylon membrane and diluted 10× to 0.11 mg/mL.

Instrumentation and Columns:

• Alliance HPLC with 2489 UV/Vis Detector (XBridge BEH C8, 5 µm, 4.6×150 mm)
• ACQUITY Arc UHPLC with 2998 PDA Detector (XBridge BEH C8 XP, 2.5 µm, 3.0×75 mm)
• ACQUITY UPLC H-Class with PDA Detector (CORTECS UPLC C8, 1.6 µm, 2.1×50 mm)

Analytical Conditions:

• Mobile phase: acetonitrile:water:acetic acid (45:54:1, v/v/v)
• Detection at 254 nm; column at 30 °C; sample at 10 °C
• Flow rates: 1.20 mL/min (HPLC), 1.02 mL/min (UHPLC), 0.74 mL/min (UPLC)
• Injection volumes scaled to column dimensions (20 µL, 4.3 µL, 1.4 µL)
• Data processed in Empower 3 FR5

Main Results and Discussion

All methods met USP criteria (assay 90–110%, RSD ≤2%, tailing ≤2.0). Transitioning to UHPLC yielded ~4× shorter run times and solvent reduction; UPLC enabled ~8× faster analysis and ~13× lower mobile phase consumption. In the UPLC lifetime study (10 000 injections), no significant pressure rise or tailing increase was observed, confirming column robustness.

Benefits and Practical Applications

• Enhanced laboratory throughput through shorter runs.
• Major cost savings in solvent procurement and waste management.
• Regulatory compliance maintained without full method revalidation.

Future Trends and Potential Applications

Continued advances in sub-2 µm particle technologies and column hardware may further reduce analysis time and solvent usage. Integration with automated sample handling and advanced data analytics will streamline routine QC assays across pharmaceutical and industrial labs.

Conclusion

Modernizing the USP naproxen sodium assay from HPLC to UHPLC and UPLC affords marked improvements in speed, cost efficiency, and sustainability while preserving analytical performance and regulatory compliance. The demonstrated stability over 10 000 injections underscores the method’s robustness for high-throughput QC environments.

References

1. Baksam V, Nimmakayala S, Devineni SR, Muchumarri RM, Shandilya S, Kumar P. Isolation and Characterization of Thermal Degradation Impurity in Brimonidine Tartrate by HPLC, LC-MS/MS, and 2D-NMR. J Pharm Biomed Anal. 2021;205:114297.
2. Aliyu AO, Garba S, Balogun LO, Awe FE. Quality Assessment of Selected Brands of Amoxicillin–Clavulanate in Kaduna, Nigeria. J Pharm Biol Sci. 2021;16:33–40.
3. Monisha ST, Ela KN, Islam R, Ether SA, Rahman FI. Quality Attributes of Rosuvastatin Calcium Tablets in US and Bangladesh Markets. J Pharm Res Int. 2021;33:46–55.
4. United States Pharmacopeia. General Chapter <621> Chromatography. 2021.
5. Swann T, Nguyen JM. USP Method Modernization Using “Equivalent L/dp” and “Equivalent N” with CORTECS C8 Columns. Waters Appl Note. 2016;720005666EN.
6. United States Pharmacopeia. Naproxen Sodium Tablets Monograph. 2021.
7. Berthelette KD, Summers M, Fountain KJ. Improving Resolution Using CORTECS UPLC Columns. Waters Appl Note. 2013;720004737EN.
8. Berthelette KD, Nguyen JM, Turner JE. Peak Capacity with CORTECS Columns on Agilent 1290. Waters Appl Note. 2021;720007250EN.
9. Shia JC, Yabu M, Tran KV, Young M. Paraquat and Diquat Drinking Water Analysis Using CORTECS UHPLC HILIC. Waters Appl Note. 2013;720004732EN.
10. Danaceau JP, Chambers EC, Fountain KJ. CORTECS C18 and XBridge BEH Phenyl XP Columns for Pain Drug Panel. Waters Appl Note. 2014;720005185EN.
11. Berthelette KD, Fountain KJ, Summers M. Improving Method Robustness for Pharmaceutical Formulations. Waters Appl Note. 2013;720004807EN.
12. Sigma-Aldrich. Acetonitrile for HPLC, Gradient Grade ≥99.9%. 2021.
13. Sigma-Aldrich. Water Suitable for HPLC. 2021.
14. Sigma-Aldrich. Glacial Acetic Acid, HPLC Grade. 2021.
15. Cost calculation for mobile phase based on reagent pricing and composition.