Examples of USP Method Modernizations Using “Equivalent L/dp” and “Equivalent N” Allowed Changes with CORTECS C8 Columns

Significance of the Topic

Fenoprofen and chlorthalidone monographs in the USP framework often rely on fully porous columns that result in long run times and high solvent use. Updating these methods can greatly improve sample throughput and reduce consumption of organic solvents.

Objectives and Study Overview

This study aimed to modernize the USP monographs for fenoprofen and chlorthalidone using the Equivalent L/dp and Equivalent N approaches. By employing solid-core CORTECS C8 and CORTECS UPLC C8 columns, the goal was to shorten analysis times and lower solvent volumes while maintaining compliance with USP criteria.

Methodology and Instrumentation

• Monograph methods were transferred from fully porous ZORBAX C8 and XBridge BEH C8 columns to CORTECS C8 (2.7 µm) and CORTECS UPLC C8 (1.6 µm) solid-core columns.
• The Equivalent L/dp approach preserves the column length to particle diameter ratio within –25% to +50% of the original, while Equivalent N maintains theoretical plate count within the same limits.
• Instrumentation included an Alliance HPLC system for reference methods and an ACQUITY UPLC H-Class system with AutoBlend for modernized runs.
• Mobile phases and flow rates were scaled to maintain pressure limits: fenoprofen runs used 50:49.6:0.4 acetonitrile : water : phosphoric acid at scaled flow rates, whereas chlorthalidone runs used 0.01 M ammonium phosphate : methanol at adjusted flow.

Main Results and Discussion

• Fenoprofen separation time was reduced by 93% and solvent consumption by 95% using a CORTECS UPLC C8 3.0×30 mm column under Equivalent N conditions.
• Chlorthalidone method modernization achieved a six-fold run time reduction and up to 88% solvent savings with a CORTECS UPLC C8 3.0×75 mm column under Equivalent L/dp criteria.
• All modernized columns met USP resolution and plate count specifications, demonstrating effective transfer of compendial methods to high-efficiency solid-core formats.

Benefits and Practical Applications

• Significant increase in laboratory throughput due to faster separations.
• Major reduction in organic solvent usage aligns with green chemistry goals and lowers operational costs.
• Flexibility to select column dimensions that match available instrumentation classes (HPLC, UHPLC, UPLC) while preserving method performance.

Future Trends and Applications

The success of Equivalent L/dp and Equivalent N guidelines with solid-core columns paves the way for broader USP method modernizations across various analytes. Continued integration of sub-2 µm particle technologies and expanded application in regulated industries will further optimize analytical workflows.

Conclusion

The study confirms that USP monograph methods for fenoprofen and chlorthalidone can be successfully modernized using CORTECS solid-core columns under Equivalent L/dp and Equivalent N criteria. This approach delivers faster, greener, and compliant methods ideal for contemporary analytical laboratories.

References

1. USP38-NF33 Monograph: Fenoprofen.
2. USP38-NF33 Monograph: Chlorthalidone.
3. USP38-NF33 General Chapter <621>.
4. Swann T and Nguyen J. USP Method Modernization Using Equivalent L/dp and Equivalent N Allowed Changes with CORTECS C8 and CORTECS UPLC C8 Columns. Waters Application Note 720005666EN (2016).