USP Method for the Impurity Analysis of Loratidine Using CORTECS C8 Columns

Importance of the topic

Modernization of pharmacopeial methods is critical to meet today’s demands for higher sample throughput and lower environmental impact. By updating United States Pharmacopeia (USP) procedures to advanced column technologies, laboratories can dramatically reduce analysis time and solvent consumption while maintaining compendial compliance.

Objectives and study overview

This work demonstrates the transfer of the official USP monograph for the impurity analysis of loratadine onto CORTECS C8 columns with smaller particle sizes. The study compares performance on three column formats spanning 5 µm, 2.7 µm, and 1.6 µm particles according to USP General Chapter <621> guidelines on column configuration.

Methodology and instrumentation

Chromatographic separations were conducted on an ACQUITY UPLC H-Class System using Empower 3 software. Key components and conditions included:

• XBridge BEH C8, 5 µm, 4.6×150 mm
• CORTECS C8, 2.7 µm, 3×100 mm
• CORTECS UPLC C8, 1.6 µm, 2.1×50 mm
• Mobile phase: acetonitrile : methanol : 0.01 M dibasic K₂HPO₄ (6 : 6 : 7), pH 7.2 (phosphoric acid)
• Isocratic elution at 254 nm UV detection
• Flow rates scaled from 1.0 mL/min (5 µm) down to 0.6 mL/min (1.6 µm); injection volumes from 15 µL to 1 µL

Key results and discussion

System suitability parameters were met or exceeded for all columns. Compared to the reference 5 µm column (loratadine retention ~9.6 min, resolution 2.7, RSD 0.74%), core-shell and sub-2 µm formats delivered:

• 2.7 µm CORTECS C8: loratadine at ~2.9 min; resolution 3.5; RSD 0.51%; four-fold less solvent
• 1.6 µm CORTECS UPLC C8: loratadine at ~1.4 min; resolution 2.5; RSD 0.32%; ten-fold less solvent

The column length-to-particle size ratio (L/dp) was verified to be within ±25 % to +50 % of the original (22 500–45 000), ensuring method compliance.

Benefits and practical applications

The adoption of CORTECS C8 phases yields several advantages:

• Up to tenfold reduction in analysis time
• Major decrease in organic solvent usage
• Improved peak resolution and precision
• Compatibility with existing HPLC and UPLC platforms under USP <621> allowances

These improvements translate into higher laboratory productivity and lower operational costs.

Future trends and opportunities

As core-shell and sub-2 µm technologies become more accessible, further modernization of other USP monographs is expected. Integration with high-throughput workflows, coupling to mass spectrometry, and application to complex formulations represent promising areas of expansion.

Conclusion

Modern CORTECS C8 columns enable a straightforward update of the USP loratadine impurity method, delivering faster separations and dramatic solvent savings without compromising official acceptance criteria. This approach exemplifies how chromatographic innovation can align regulatory compliance with the needs of contemporary pharmaceutical analysis.

References

1. CORTECS Columns Brochure (720004675en).
2. USP38-NF33 S2 Monograph: Loratadine.