Quality-by-Design-Driven RP-HPLC Method Development and Validation for Impurity Analysis of Elexacaftor, a Cystic...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Elexacaftor (ELX) is a crucial pharmaceutical compound.
• Accurate impurity profiling is essential for drug safety and efficacy.
• Existing analytical methods may require optimization for comprehensive impurity determination.

Purpose of the Study:

• To develop and validate a robust RP-HPLC method for determining impurities in Elexacaftor (ELX).
• To establish a stability-indicating assay for quality control in bulk drug manufacturing.

Main Methods:

• Utilized a straightforward, stability-indicating RP-HPLC technique.
• Employed an XBridge Shield RP 18 column with a gradient elution of methanol, acetonitrile, 2-propanol, and potassium dihydrogen orthophosphate buffer.
• Optimized photodiode array detection at 220 nm with a 0.7 mL/min flow rate over a 90-minute run time at 27 °C.

Main Results:

• Successfully separated and quantified six known impurities with appropriate resolution and peak shape.
• The method demonstrated linearity, accuracy, specificity, selectivity, and exactness across a wide range (LOQ to ~0.45% for impurities, LOQ to ~120% for ELX).
• Method robustness was confirmed using Design of Experiments (DoE) within a Quality by Design (QbD) framework.

Conclusions:

• The developed RP-HPLC method is validated according to ICH guidelines, proving suitable for Elexacaftor (ELX) impurity analysis.
• The method's stability under various stress conditions (acid/base hydrolysis, oxidation, thermal, photolytic) confirms its suitability for process development and quality assurance.
• This validated assay is instrumental for ensuring the quality and safety of bulk Elexacaftor (ELX) drug substance.