USP Method Transfer of Ziprasidone HCl from HPLC to UPLC

Significance of Topic

The transition from traditional HPLC methods to UPLC technology enables significant improvements in analytical efficiency, throughput, and cost reduction. In pharmaceutical quality control, compendial monographs such as the USP method for ziprasidone HCl serve as standardized assays for drug substances and products. Adapting these methods to sub-2 µm UPLC platforms can accelerate routine testing while maintaining compliance with official assay criteria.

Objectives and Study Overview

This work demonstrates the systematic transfer of the USP HPLC assay for ziprasidone HCl to a UPLC format. It aims to verify equivalence of chromatographic performance, meet system suitability requirements, and evaluate long-term column stability under high-throughput conditions using both standard and capsule formulations of ziprasidone.

Methodology and Instrumentation

Samples were prepared at 0.23 mg/mL in a 60:40 methanol–water diluent and filtered through a 0.2 µm PTFE membrane. The original USP HPLC conditions used a 4.6 × 150 mm, 5 µm XBridge C8 (L7) column operated isocratically with 25 mM potassium phosphate buffer (pH 3.0) and methanol (60:40) at 1.5 mL/min, detected at 229 nm. For UPLC, conditions were scaled to a 2.1 × 50 mm, 1.7 µm BEH C8 column at 0.6 mL/min. Method parameters were calculated using an online UPLC Columns Calculator and implemented on an ACQUITY UPLC H-Class system controlled by Empower 2 CDS.

Key Results and Discussion

Comparison of five replicate injections for both HPLC and UPLC showed retention times of ~3.9 min versus ~0.7 min, respectively, with tailing factors and area precision well within USP limits (tailing < 2.5; %RSD < 2%). UPLC delivery reduced run time by 85% (1.5 vs 10 min) and cut solvent and sample volume usage by 93%. A routine-use study on the UPLC column involved over 2,400 sequential injections of standard and capsule samples. Throughout this extended sequence, column backpressure and tailing factors remained stable, and system suitability criteria continued to meet compendial requirements.

Benefits and Practical Applications

• Substantial time savings increase sample throughput in QC labs.
• Reduced solvent consumption and sample injection lower operating costs.
• Robust column performance supports large batch analyses without frequent replacement.
• Direct compliance with USP monograph criteria ensures regulatory acceptability.

Future Trends and Opportunities

Ongoing trends include wider implementation of UPLC for routine assays across diverse drug classes, further miniaturization of chromatographic systems, and integration with automated sample preparation platforms. Advances in column chemistries and buffer-compatible stationary phases will expand applications for complex formulations. Additionally, digital tools for method translation and real-time monitoring will streamline method validation and transfer processes.

Conclusion

The transfer of the USP ziprasidone HCl assay from HPLC to UPLC was achieved successfully, delivering equivalent chromatographic performance while offering dramatic improvements in speed, solvent savings, and throughput. The UPLC column demonstrated exceptional stability over extended use, confirming its suitability for high-volume quality control testing.

References

1. USP Monograph, Ziprasidone HCl, USP34–NF29, 4631, United States Pharmacopeial Convention, effective May 1, 2011.
2. Jones MD, Alden P, Fountain KJ, Aubin A. Implementation of Methods Translation between Liquid Chromatography Instrumentation. Waters Application Note, 2010, Part No. 720003721EN.