UPLC-LCMS-Based Method Development, Validation, Forced Degradation, and Impurity Profiling of Nirogacestat Drug...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Science

Background:

• Establishing a robust stability-indicating method is crucial for pharmaceutical quality assurance.
• Nirogacestat stability and impurity profiling require a reliable analytical technique.

Purpose of the Study:

• To develop and validate a novel Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) method for Nirogacestat.
• To assess Nirogacestat's stability and impurity profile under various ICH-guided stress conditions.

Main Methods:

• Forced degradation studies were conducted using acid, base, oxidative, thermal, photolytic, and reductive stress conditions.
• Chromatographic separation was performed using an Acquity UPLC BEH Shield RP-18 column with a specific mobile phase.
• Method validation encompassed selectivity, linearity, accuracy, precision, and robustness assessments.

Main Results:

• The UPLC-MS method demonstrated excellent linearity (r² = 0.999) and met all validation parameters.
• Distinct degradation products were identified under various stress conditions, with alkaline conditions showing minimal degradation.
• The method successfully separated Nirogacestat from its impurities, confirmed by mass spectrometry.

Conclusions:

• The validated UPLC-MS method is sensitive, selective, and robust for Nirogacestat impurity profiling.
• This stability-indicating assay complies with ICH guidelines and is suitable for quality control and regulatory submissions.
• The method enhances the understanding of Nirogacestat's degradation, supporting formulation development and ensuring drug safety.