Development and Validation of a Stability-Indicating High-Performance Liquid Chromatography Method Coupled With a...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Quality by Design (QbD)

Background:

• Haloperidol oral solutions require stability-indicating methods for quality control.
• Traditional analytical method development can be subjective and time-consuming.
• Analytical Quality-by-Design (aQbD) offers a systematic approach to enhance method robustness.

Purpose of the Study:

• To develop and validate a stability-indicating HPLC-DAD method for haloperidol quantification in oral solutions.
• To apply aQbD principles for systematic method development and optimization.
• To establish the method's robustness and reliability for routine stability monitoring.

Main Methods:

• Utilized analytical Quality-by-Design (aQbD) principles, including defining the analytical target profile and risk analysis.
• Employed factorial and Box-Behnken designs for critical method parameter selection and optimization.
• Validated the method according to ICH guidelines, assessing selectivity, accuracy, and precision within the established method operable design region.

Main Results:

• The HPLC-DAD method demonstrated stability-indicating capability, showing significant haloperidol degradation under acidic and alkaline conditions.
• Optimization using Box-Behnken design yielded robust regression models with high R²-adjusted values (>0.85).
• The method proved selective, accurate, and precise across the defined operational range, with established Normal Operating Conditions (NOCs).

Conclusions:

• The aQbD-based HPLC-DAD method is robust, reliable, and suitable for stability monitoring of haloperidol oral solutions.
• This systematic approach reduces subjectivity and enhances the overall quality and dependability of the analytical procedure.
• The established method operable design region ensures consistent performance under routine laboratory conditions.