LC-PDA & LC-MS/MS approach of Daprodustat: forced degradation study

Area of Science:

• Analytical Chemistry
• Pharmaceutical Science

Background:

• Daprodustat is a hypoxia-inducible prolyl hydroxylase inhibitor used to treat anemia in Chronic Kidney Disease (CKD) patients.
• Ensuring the stability of pharmaceutical compounds is crucial for patient safety and therapeutic efficacy.

Purpose of the Study:

• To develop and validate a stability-indicating RP-HPLC method for daprodustat.
• To investigate the degradation products of daprodustat under various stress conditions.

Main Methods:

• A stability-indicating RP-HPLC method was developed and validated according to ICH Q2 guidelines.
• Chromatographic separation was performed on a Zorbax SB C18 column using a mobile phase of ethanol and formic acid (20:80, v/v) at a flow rate of 1 mL/min.
• Forced degradation studies were conducted as per ICH Q1A (R2) guidelines, and degradation products were analyzed using HPLC coupled with mass spectrometry (SCIEX QTRAP 5500).

Main Results:

• Three degradation products were identified from forced degradation studies.
• The probable structures and fragmentation patterns of these degradation products were elucidated using mass spectrometry.
• The developed method demonstrated the ability to clearly depict daprodustat's stability under various environmental factors.

Conclusions:

• The developed RP-HPLC method is stability-indicating, cost-effective, and time-efficient for assessing daprodustat stability.
• This study contributes to impurity profiling and ensures the quality control of daprodustat.
• The findings support the safe and effective use of daprodustat in treating anemia in CKD patients.