High Performance USP Analysis of Ziprasidone Capsules on an Alliance HPLC System

Importance of the Topic

The accurate quantification of ziprasidone in pharmaceutical formulations is essential for ensuring drug safety and regulatory compliance. The United States Pharmacopeia compendial methods provide standardized procedures that generic drug manufacturers and quality control laboratories rely on for consistent assay performance. Robust chromatographic techniques, such as HPLC, are indispensable in routine analysis to meet stringent accuracy and precision requirements.

Objectives and Overview of the Study

This study aimed to demonstrate the application of the USP compendial method for ziprasidone HCl analysis on a Waters Alliance HPLC System. Two sample types, a standard solution and commercial ziprasidone capsules, were evaluated using hybrid column technology. Key objectives included assessing method suitability criteria—such as peak symmetry and injection repeatability—and verifying reproducibility under the specified chromatographic conditions.

Methodology and Used Instrumentation

The USP monograph prescribes an L7 type column; an equivalent XBridge C8 hybrid column was selected via Waters Column Selectivity Chart to enhance robustness across varied pH ranges. Chromatographic separation was performed on an Alliance HPLC System equipped with a 2998 Photodiode Array Detector. The mobile phase and gradient followed the USP protocol unmodified. System suitability was tested with five replicate injections for both standard and capsule samples, monitoring retention time, peak area, and USP tailing factor.

Main Results and Discussion

Both standard and capsule analyses exhibited sharp, well-defined peaks at approximately 3.88 minutes. Repeatability metrics met USP criteria: retention time %RSD was 0.14% for standards and 0.05% for capsules; peak area %RSD was 0.03% and 0.11%, respectively. All USP tailing factors remained below 1.5. The integrated fluidic design and independent pump drives of the Alliance system minimized dispersion and solvent compressibility effects, resulting in highly consistent chromatographic performance.

Benefits and Practical Applications of the Method

• Ensures compliance with USP suitability requirements for ziprasidone assays.
• Hybrid column technology improves column lifetime and stability under buffered conditions.
• Automated and precise fluidics reduce instrument downtime and maintenance.
• Ideal for high-throughput quality control in pharmaceutical development and production.

Future Trends and Possibilities of Utilization

• Expansion of hybrid particle column chemistries for broader analyte compatibility.
• Integration with mass spectrometry detectors for enhanced sensitivity and specificity.
• Adoption of green chromatography practices, including alternative solvents and reduced waste.
• Advanced automation and data analytics for real-time method optimization and compliance reporting.

Conclusion

The application of the USP compendial method on the Waters Alliance HPLC System with an XBridge C8 column demonstrated high precision, accuracy, and reproducibility for ziprasidone capsule analysis. This approach supports routine quality control processes by delivering reliable results while minimizing operational complexity and instrument maintenance.

Used Instrumentation

• Waters Alliance HPLC System
• Waters XBridge C8 Hybrid Column (L7 equivalent)
• Waters 2998 Photodiode Array Detector