Transfer of USP Assay for Quetiapine Fumarate Across Different Liquid Chromatographic Systems

Significance of the Topic

The accurate determination of active pharmaceutical ingredients is essential for quality control. The USP assay for quetiapine fumarate is a well-established HPLC method. Demonstrating successful transfer of this method to UHPLC and UPLC platforms can enhance laboratory throughput and flexibility while maintaining regulatory compliance.

Objectives and Study Overview

• Evaluate the USP quetiapine fumarate assay on three different LC systems under monograph conditions.
• Compare system suitability parameters and reproducibility across platforms.
• Assess assay performance using an unknown sample.

Methodology and Instrumentation

The USP monograph method was run isocratically on a XBridge BEH C8 column (4.6×250 mm, 5 µm) at 25 °C.

• Mobile phase: methanol : acetonitrile : 2.6 g/L dibasic ammonium phosphate buffer (54 : 7 : 39) at pH 6.5.
• Flow rate 1.3 mL/min; run time 15 min; detection at 230 nm with 4.8 nm resolution.
• Injection volume 50 µL; sample temperature 4 °C; data captured at 10 Hz using Empower 3 software.
• Instruments: Alliance e2695 HPLC with PDA, ACQUITY Arc UHPLC with CH-30A and PDA, ACQUITY UPLC H-Class PLUS with PDA detector.

Main Results and Discussion

System suitability criteria from USP <621> include resolution ≥ 1.5 between quetiapine desethoxy and quetiapine, tailing factor ≤ 2.0, and RSD ≤ 2.0 %.

• Resolution: 2.4 (HPLC), 2.7 (UHPLC), 2.6 (UPLC).
• Tailing factor: 1.2, 1.1, and 1.1 respectively.
• Area RSD ≤ 0.09 %; retention time RSD ≤ 0.27 % across all systems.

All platforms met USP criteria with high precision. An unknown sample assay returned 107 %–108 % quetiapine fumarate, outside the USP expected range (98 %–102 %) but reproducible across instruments. Further investigation by peak purity assessment or mass spectrometry is advised to identify potential interferences.

Benefits and Practical Applications

• Confirms that legacy USP methods can operate on modern low dispersion LC systems.
• Allows labs to migrate methods to higher throughput platforms without full revalidation.
• Enables improved sample throughput and efficient resource utilization in QA/QC workflows.

Future Trends and Potential Applications

• Coupling assay methods with mass spectrometric detection for increased specificity.
• Use of shorter columns and advanced stationary phases to reduce runtime.
• Implementation of automation and real-time system suitability monitoring.

Conclusion

The USP quetiapine fumarate assay was successfully transferred across three Waters LC platforms, meeting all system suitability and repeatability requirements. Consistent assay performance supports flexible platform interchangeability in pharmaceutical analysis.

References

• Hong P, McConville PR. Dwell Volume and Extra-Column Volume: What Are They and How Do They Impact Method Transfer. Waters White Paper, 2016.
• United States Pharmacopeia. Quetiapine Fumarate Monograph, USP 40-NF35 S1.
• United States Pharmacopeia. General Chapter <621> Chromatography, USP 40-NF35 S1.
• Snyder LR, Kirkland JJ, Dolan JW. Introduction to Liquid Chromatography. 3rd Ed. Wiley, 2010.