Useful Strategies for Modernizing USP Methods - Application Compendium

Significance of the topic

Pharmaceutical analysis is evolving to meet demands for higher accuracy, safety and sustainability. Modernizing U.S. Pharmacopeia (USP) monographs and general chapters with advanced techniques such as high-performance liquid chromatography (HPLC) and ion chromatography (IC) ensures laboratories maintain compliance, improve robustness and reduce environmental impact.

Objectives and overview of the compendium

This application compendium presents real-world strategies for updating small-molecule analytical methods in alignment with global USP modernization initiatives. Eight application notes illustrate approaches to liquid chromatography modernization, sustainable cost-saving enhancements, adoption of USP <621> revisions and optimization of excipient and API impurity analyses.

Methodology and instrumentation

Methods follow revised USP <621> guidelines, allowing adjustments to column dimensions, particle sizes, flow rates and gradients without full revalidation. Key instrumentation includes:

• Agilent 1260 Infinity II LC system
• Agilent InfinityLab Poroshell 120 EC-C8, ZORBAX Eclipse Plus C18 and RRHD columns
• Agilent 8850 GC-FID coupled with 8697 headspace sampler

Carrier gas transitions (helium to hydrogen) and use of superficially porous particles reduce run times and solvent consumption.

Main results and discussion

Implementing superficially porous particle columns and UHPLC systems achieved reductions in analysis time from 60 to as little as 8.6 minutes and solvent savings up to 92%. Gradient method transfers to smaller columns cut run times by over 50% and reduce hazardous solvent waste. Revisions to USP <621> enabled seamless method updates—e.g., acetaminophen/caffeine and ceftizoxime assays—without revalidation. Impurity profiling of diphenhydramine HCl demonstrated higher resolution and faster throughput.

Benefits and practical applications of the method

• Enhanced laboratory throughput and operational efficiency
• Significant reductions in solvent use, waste and energy consumption
• Regulatory compliance through USP-approved adjustments without revalidation
• Improved data quality, robustness and method flexibility

Future trends and possibilities

Continued adoption of green chromatography, integration of automated and risk-based method adjustments, and expansion of digital tool support will drive further efficiency gains. Ongoing harmonization between USP, FDA and other pharmacopeias will streamline global compliance and foster innovation.

Conclusion

This compendium demonstrates that leveraging advanced chromatographic technologies and updated USP guidelines can transform legacy methods into high-performance, sustainable workflows. Collaboration among laboratories, regulatory bodies and technology partners is essential to sustain progress and ensure product quality.

References

• USP General Chapter <621> Chromatography, U.S. Pharmacopeia
• Agilent Application Notes: Modernizing USP Small-Molecule Methods, 2025