Ultra-high Speed Analysis of Ibuprofen within USP <621> Allowed Limits by Nexera Method Scouting

Importance of the Topic

High-speed, high-throughput HPLC methods are critical in pharmaceutical analysis to accelerate drug development, ensure compliance with pharmacopeial standards, and reduce solvent usage and waste generation. The adoption of small-particle and core-shell columns, coupled with allowed method adjustments under USP <621> and EP <2.2.46>, offers a pathway to improve laboratory productivity without extensive revalidation.

Objectives and Overview of the Study

This application note evaluates ultra-high-speed analysis of ibuprofen within the USP <621> limits using the Shimadzu Nexera Method Scouting System. It compares a conventional C18 column with core-shell Kinetex XB-C18 columns of different lengths and assesses the impact of increased flow rate on analysis time and system suitability.

Methodology and Instrumentation

Method development was automated on the Nexera Method Scouting System, screening mobile phases and columns without manual intervention. Key instrumentation and conditions:

• Columns: Shim-pack VP-ODS (250 mm × 4.6 mm, 4.6 µm); Kinetex XB-C18 (100 mm and 75 mm × 4.6 mm, 2.6 µm)
• Detector: SPD-20AV UV-Vis at 254 nm with high-sensitivity semi-micro cell
• Autosampler: SIL-30AC (injection range 0.1–50 µL)
• Mobile Phase: 40% 1% chloroacetic acid (pH 3.0)/60% acetonitrile (v/v)
• Flow Rates: 2.0 mL/min and 3.0 mL/min
• Column Temperature: 30 °C; Injection Volume: 10 µL

Main Results and Discussion

• Switching from a 250 mm conventional column to a 100 mm core-shell reduced cycle time by ~75% (from 12.0 min to 2.3 min), while a 75 mm core-shell achieved ~88% reduction (1.5 min).
• Increasing flow to 3.0 mL/min further shortened run time by over 30% without loss of resolution.
• All configurations met USP system suitability: resolution >2.5, symmetry factors <2.5, and RSD <2.0% for retention time and peak area.
• Solvent consumption dropped by over 75% with core-shell columns.
• Impurity test showed related compound C at 0.039%, well below the 0.1% limit.
• Repeatability at 0.1 µL injection yielded %RSD ~0.8% for peak areas, demonstrating excellent precision.

Benefits and Practical Applications

• Substantial throughput gains support faster quality control and R&D workflows in pharmaceutical laboratories.
• Lower solvent use and waste disposal costs enhance sustainability and reduce operating expenses.
• Allowed USP/EP adjustments facilitate method transfer and speeding of new drug analysis without full revalidation.

Future Trends and Potential Uses

• Wider adoption of automated method scouting to streamline chromatographic method development.
• Integration of core-shell UHPLC with LC-MS for comprehensive impurity profiling.
• Exploration of sub-2 µm superficially porous particles to further reduce analysis times.
• Implementation of AI-driven optimization routines for rapid, data-driven method refinement.

Conclusion

The study demonstrates that leveraging core-shell columns and USP-approved parameter adjustments dramatically accelerates ibuprofen analysis, meets stringent system suitability criteria, and reduces solvent consumption. Automated method scouting further enhances productivity, presenting a robust approach for routine pharmaceutical testing.

Reference

• USP Monograph for Ibuprofen, USP 35–NF 30, 2012