Stability-indicating UPLC method for determining related substances and degradants in dronedarone

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Accurate quantification of active pharmaceutical ingredients (APIs) and their impurities is crucial for drug quality and patient safety.
• Dronedarone hydrochloride (DRO) is an antiarrhythmic drug requiring robust analytical methods for quality control.

Purpose of the Study:

• To develop and validate a simple, sensitive, and reproducible ultra-performance liquid chromatography (UPLC) method for the quantitative determination of dronedarone hydrochloride (DRO).
• To assess the method's applicability for quantifying related substances and performing assays of drug substances and pharmaceutical dosage forms.
• To establish the method's stability-indicating capability by evaluating dronedarone hydrochloride under various stress conditions.

Main Methods:

• Ultra-performance liquid chromatography (UPLC) coupled with photodiode array (PDA) detection was employed.
• Chromatographic separation was achieved using an Acquity UPLC BEH C8 column (100 mm x 2.1 mm, 1.7 µm) with gradient elution in a 10.0 min run time.
• Method validation was performed according to International Conference on Harmonization (ICH) guidelines, assessing specificity, linearity, accuracy, precision, LOD, LOQ, and robustness.

Main Results:

• The method demonstrated excellent linearity (correlation coefficient >0.9995) and high precision (RSD <2.5%) for repeatability and intermediate precision.
• The UPLC-PDA method effectively resolved dronedarone hydrochloride from 11 potential impurities and degradation products with a resolution greater than 2.0.
• Dronedarone hydrochloride showed significant degradation under acidic and basic conditions but remained stable under oxidative, hydrolytic, thermal, and photolytic stress, confirming the method is stability-indicating.

Conclusions:

• A validated UPLC-PDA method provides a simple, sensitive, and reproducible means for the quantitative determination of dronedarone hydrochloride in drug substances and pharmaceutical formulations.
• The developed method is suitable for routine quality control, including assay, related substances, and stability testing.
• The method's ability to resolve degradation products confirms its utility as a stability-indicating assay for dronedarone hydrochloride.