High Speed Analysis of Budesonide in Accordance with Chapter 621 in USP 40

Importance of the Topic

High-performance liquid chromatography (HPLC) methods specified in the United States Pharmacopeia (USP) often rely on conventional 5 µm columns, leading to long runtimes, high solvent consumption and elevated operational costs. Advances in ultra-high-performance liquid chromatography (UHPLC) and sub-2 µm column packing enable faster separations while maintaining resolution, supporting more efficient pharmaceutical quality control.

Objectives and Study Overview

This study aimed to demonstrate a rapid, USP Chapter 621-compliant isocratic method for the analysis of budesonide, a corticosteroid used in asthma, allergy and dermatological treatments. By modifying column dimensions and flow parameters within allowable USP ranges, the investigation compared the traditional USP method with two accelerated approaches.

Methodology and Analytical Conditions

Isocratic separation employed a phosphate buffer (pH 3.2) and acetonitrile (68:32 v/v) on three Shim-pack GIST C18 columns:

• 4.6 × 150 mm, 5 µm (original USP method)
• 3.0 × 100 mm, 3 µm
• 3.0 × 50 mm, 2 µm

The L/dp ratio was maintained within −25% to +50% of the original. Flow rates were adjusted per USP formula to constant linear velocity: 1.50 mL/min for 5 µm, 1.00 mL/min for 3 µm and 0.78 mL/min for 2 µm columns. Injection volumes were 20 µL, 5 µL and 1 µL respectively. Detection was performed at 254 nm.

Instrumentation Used

• Shimadzu Prominence-i LC-2030C Plus system
• Shim-pack GIST C18 analytical columns (5 µm, 3 µm, 2 µm variants)

Main Results and Discussion

Both accelerated methods achieved shorter retention times for budesonide while satisfying system suitability: resolution ≥1.5, relative retention constant at 1.1, and USP plate counts above 7 400. The fast methods reduced analysis time by approximately 40–60% compared to the original 5 µm column, without compromising peak separation or reproducibility.

Benefits and Practical Applications

• Reduced solvent usage lowers running costs and environmental impact.
• Higher sample throughput accelerates QC workflows in pharmaceutical laboratories.
• Maintained compliance with USP Chapter 621 ensures method robustness.

Future Trends and Potential Applications

Ongoing developments in core-shell and sub-2 µm particle technology will further decrease runtime and solvent consumption. Integration with mass spectrometry and automated sampling will enhance sensitivity and throughput. Green chromatography approaches and miniaturized flow cells will support sustainable practices.

Conclusion

Modifying USP budesonide HPLC conditions with reduced column dimensions and optimized flow rates on the Prominence-i system delivers rapid, compliant analysis with significant time and cost savings, demonstrating the feasibility of high-speed USP methods in routine pharmaceutical testing.

References

• 1. Budesonide. National Center for Biotechnology Information. MeSH ID: D001059.
• 2. Application News No. L464, Shimadzu High Speed Analysis of Budesonide, 2018.
• 3. USP General Chapter 621, USP 40–NF 35, First Supplement.
• 4. USP Monograph: Budesonide, USP 34–NF 29, First Supplement.