Streamlined Method Validation for Analysis of Formoterol Fumarate and Budesonide in Metered Dose Inhaler with Empower Method Validation Manager Software

Importance of the Topic

The combination of formoterol fumarate and budesonide in metered dose inhalers is vital for managing asthma and COPD. Reliable analytical methods ensure consistent dosing, regulatory compliance, and patient safety.

Objectives and Study Overview

This study aimed to validate a UPLC method for simultaneous quantitation of formoterol fumarate and budesonide using Empower Method Validation Manager software. Key validation parameters aligned with regulatory guidelines were evaluated to confirm method suitability for quality control of inhaler products.

Methodology and Instrumentation

The assay employed an ACQUITY UPLC H-Class PLUS system with BEH C18 column, a gradient of ammonium acetate buffer and acetonitrile, and detection by ACQUITY UPLC PDA and QDa mass detector with ESI+ mode. Empower 3 MVM software managed protocol creation, data acquisition, statistical analysis, and reporting.

Main Results and Discussion

• System suitability met criteria: retention time RSD <1%, area RSD <2%, resolution ≥2, tailing ≤1.5.
• Linearity across 80–120% concentration range yielded R2 ≥0.999 for both analytes.
• Accuracy recoveries ranged 97.8–101.5% with RSD ≤1.42% at 80, 100, and 120% levels.
• Repeatability and intermediate precision showed recoveries within ±5% and RSD ≤2% across analysts.
• Specificity confirmed by UV and MS spectral purity, demonstrating no coelution with related compounds.
• Robustness under ±2 °C and ±0.05 mL/min flow variations maintained resolution ≥2.
• Continuous performance verification via control charts enabled trend monitoring of critical parameters.

Benefits and Practical Applications

The integrated software platform streamlined validation workflows, ensured data integrity, reduced manual calculations, and facilitated electronic sign-off. The validated UPLC method supports routine QC testing of inhaler formulations with high confidence.

Future Trends and Applications

• Expansion of software-driven analytics with AI-powered data review and anomaly detection.
• Adoption of the analytical procedure lifecycle model for ongoing method optimization.
• Integration of real-time mass spectrometric data to enhance specificity and impurity profiling.
• Development of digital workflows for end-to-end method management and compliance.

Conclusion

The validated UPLC method using Empower MVM software meets stringent regulatory requirements for precision, accuracy, and robustness. The combined analytical and software approach enhances efficiency, ensures continuous performance verification, and supports quality control of metered dose inhaler products.

References

1. FDA. Analytical Procedures and Methods Validation for Drugs and Biologics Guidance for Industry, 2015.
2. USP<1225> Validation of Compendial Procedures, USP 36–NF31, 2013.
3. ICH Q2B. Validation of Analytical Procedures, 1996.
4. USP<1220> Analytical Procedure Lifecycle, Pharmacopeial Forum 43(1), 2017.
5. Salem et al. Journal of Chromatographic Science, 2017;55:1013–1020.
6. Alkhateeb & Rainville. Software-Assisted QbD Approach, Waters Application Note, 2019.
7. USP<621> Chromatography, USP36-NF31, 2013.
8. Maziarz et al. Continuous Performance Verification, Waters White Paper, 2019.