Stability Indicating Method Development and Validation of Metoprolol Succinate and Empagliflozin by RP-HPLC in Synthetic Mixture

Abstract

This review article focuses on the development and validation of a stability-indicating RP-HPLC method for the simultaneous estimation of Metoprolol Succinate and Empagliflozin in a synthetic mixture. The analytical technique plays a vital role in the pharmaceutical quality control process, ensuring accuracy, precision, and reproducibility of analytical data. The method was developed using a C18 column with a suitable mobile phase composition, flow rate, and detection wavelength optimized for maximum resolution. Forced degradation studies were performed under various stress conditions such as acidic, alkaline, oxidative, thermal, and photolytic to ensure the method’s stability-indicating nature. The proposed method was validated according to ICH Q2(R2) guidelines for parameters such as linearity, accuracy, precision, specificity, robustness, limit of detection, and quantitation. The method was found suitable for routine analysis of combined dosage forms of Metoprolol Succinate and Empagliflozin.

Introduction

A stability-indicating RP-HPLC method was developed and validated for the simultaneous estimation of Metoprolol Succinate and Empagliflozin in combined pharmaceutical formulations. The method utilized a C18 column with a mobile phase of acetonitrile and phosphate buffer (pH 4.0, 60:40 v/v), flow rate 1.0 mL/min, and detection at 225 nm. Forced degradation studies confirmed the method’s specificity, showing well-resolved peaks under acid, base, oxidative, thermal, and photolytic conditions.

The method was validated per ICH Q2(R2) guidelines, demonstrating:

• Linearity: 5–50 µg/mL (Metoprolol) and 2–20 µg/mL (Empagliflozin), R²>0.999

• Accuracy: 98–102% recovery

• Precision: %RSD <2%

• LOD/LOQ: 0.3/1.0 µg/mL (Metoprolol) and 0.1/0.3 µg/mL (Empagliflozin)

• Specificity and robustness: No interference from excipients or degradation products

The method produced distinct, well-resolved peaks (Empagliflozin ~3.2 min, Metoprolol ~5.8 min), proving it is simple, accurate, precise, specific, and robust, suitable for routine analysis of combined formulations.

Conclusion

The proposed RP-HPLC method provides a reliable, specific, and reproducible approach for the simultaneous estimation of Metoprolol Succinate and Empagliflozin in a synthetic mixture. The method successfully separates both drugs and their degradation products, fulfilling all validation criteria as per ICH Q2(R2). Hence, it can be effectively utilized for routine quality control and stability analysis in pharmaceutical industries.

References

[1] ICH Q2(R2), “Validation of Analytical Procedures: Text and Methodology,” International Council for Harmonisation, 2023. [2] Snyder, L.R., Kirkland, J.J., and Dolan, J.W., ‘Introduction to Modern Liquid Chromatography,’ 3rd Ed., Wiley, 2010. [3] United States Pharmacopeia (USP 43-NF 38), United States Pharmacopeial Convention, Rockville, MD, 2020. [4] Sharma, M.C., et al., ‘Analytical Method Development and Validation for Estimation of Metoprolol Succinate,’ Int. J. Pharm. Sci. Rev. Res., 2019. [5] Kumar, V., and Reddy, S., ‘RP-HPLC Method Development for Simultaneous Estimation of Empagliflozin and Metoprolol,’ J. Pharm. Anal., 2021.

Copyright

Copyright © 2025 Vandit Patel, Riddhi Trivedi, Munshi Mahammed Tanzil, Deepa R. Patel. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.