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

Daprodustat is a hypoxia-inducible prolyl hydroxylase inhibitor to treat anaemia in patients with Chronic Kidney Disease (CKD). A stability-indicating RP-HPLC method was developed and validated as per ICH Q2 guidelines. Chromatographic separation was performed on Zorbax SB C18 column (150 mm × 4.6 mm, 3.5 μ) detected at 235 nmusing a PDA detector. A mixture of ethanol and formic acid in a 20:80 (v/v) ratio was used as the mobile phase, with a flow rate of 1 mL/min. Forced degradation studies are conducted according to the International Council of Harmonization (ICH) guideline Q1A (R2). The HPLC system was coupled to a SCIEX QTRAP 5500 mass spectrometer equipped with an electrospray ionization interface to identify the plausible structures and fragmentation pattern of all the degradation products.2. Three degradation products were obtained from forced degradation. Based on the m/z values and molecular formula from the obtained MS spectra, the probable structures of degradation products were elucidated. Plausible degradation mechanism behind the formation of degradation products3. This method can clearly depict the stability of daprodustat under the influence of various environmental factors in less time with low cost. Further, this study also helps in impurity profiling studies.