Identification, Synthesis, and Characterization of N-Formyl Mirabegron: A New Degradation Product Formed by Formic...

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Organic Chemistry

Background:

• Formic acid (FAc) is a frequent reactive impurity found in pharmaceutical excipients.
• Drug stability is crucial for therapeutic efficacy and patient safety.
• Mirabegron (MB) is an active pharmaceutical ingredient susceptible to degradation.

Purpose of the Study:

• To investigate the impact of formic acid (FAc) on the stability of mirabegron (MB).
• To identify and characterize the degradation product formed in the presence of FAc.
• To understand the implications of FAc impurity on MB drug product quality.

Main Methods:

• Mirabegron-excipient compatibility studies were conducted under isothermal stress conditions (55°C).
• Degradation product formation was monitored over time (7 days).
• Liquid chromatography-mass spectrometry (LC-MS) and NMR spectroscopy (1D and 2D) were used for identification and characterization.

Main Results:

• A new degradation product, FAc-DP, was identified in mirabegron samples exposed to formic acid.
• FAc-DP formation was observed at 0.2% concentration after 7 days of stress at 55°C.
• The degradation product was synthesized and confirmed as N-formyl mirabegron (N-formyl MB).

Conclusions:

• Formic acid acts as a significant impurity that promotes mirabegron degradation.
• The formation of N-formyl mirabegron highlights a specific degradation pathway influenced by FAc.
• Control of formic acid levels in pharmaceutical excipients is essential for maintaining mirabegron stability.