LC–MS/MS characterization of stress degradation products of Ripretinib along with development and validation of a stability-indicating HPLC method for quantification of Ripretinib

The green analytical HPLC methods are highly effective for quantifying drugs because these methods reduce the usage of harmful chemicals and generate less waste leading to minimal environmental influence. Various compositions of green solvents including ethanol and water with buffers were utilized as mobile phase. The conditions that produce acceptable results were studied for valuation in terms of linearity, accuracy, precision and sensitivity. This method was applied for the sepration and characterization of degradation products (DPs) of ripretinib using LCMS/MS. The method comprises of Ascentis Express C18 (2.1 mm × 100 mm, 2.7 micron) column along with ethanol and 0.01% formic acid in water, in 65:45 (v/v) at pH 4.3 at 0.7 mL/min flow and 261 nm wavelength. Acceptable results were obtained for Ripretinib. A stress test revealed six different DPs in acid, base and peroxide breakdown tests, labelled as DP 1 to 6 based on order of elution. The applicability of MSn studies and mass fragmentation confirms DP 1 as 7-amino-3-(5-amino-2-bromo-4-fluorophenyl)-1-ethyl-1,6-naphthyridin-2(1 H)-one 1-oxide, DP 2 as 1-[5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-bromo-2-fluorop henyl]urea and DP 3 as 7-amino-3-(5-amino-2-bromo-4-fluorophenyl)-1-ethyl-1,6-naphthyridin-2(1H)-one, DP 4 as 3-(5-amino-2-bromo-4-fluorophenyl)-1-ethyl-7-(methylamino)-1,6-naphthyridin-2(1H)-one, DP 5 as {4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihyd ro-1,6-naphthyridin-3-yl]-2-fluorophenyl}carbamic ac id and DP 6 as 3-(2-bromo-4-fluoro-5-(3-phenylureido )phenyl)-1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1 ,6-naphthyridine 1-oxide. The GAPI (Green Analytical Procedure Index) and AGREE (Analytical GREEnness) tools were utilized to assesses the greenness of method. This study found that the method works well for measuring Ripretinib and characterized its DPs.