Quality by Design Based HPLC Method Development of Macitentan and its Related Compounds in Bulk Drugs

Macitentan is an oral medication, being used for the treatment of idiopathic pulmonary fibrosis. The present study describes the development of HPLC method and subsequent validation for the analysis of Macitentan, an active pharmaceutical ingredient (API) using a quality by design approach.Analysis of macitentan and its related substances was very interesting and challenging due to co-elution of critical pair 1 (impurity C and unknown impurity) and critical pair 2 (impurity D and macitentan). Objective of this study was to develop a robust high performance liquid chromatographic method for the separation of critical pair 1 and 2. An attempt was made to develop HPLC method using QbD principles. A qualityby-design (QbD) based method development can potentially lead to a more rugged method. The optimized HPLC method details: buffer consisting of sodium perchlorate (pH adjusted to 2.0 using perchloric acid) as mobile phase A and acetonitrile-buffer (8:2) v/v as mobile phase B using the column Purosphere RP 18e 100 mm × 4.6 mm ID, 3.0 µm(Make: Merck) maintained at 45 ºC with a flow rate of 1.0 mL/min in a gradient mode of elution and the UV detection was set as 220 nm.