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
Tummala Sambasiva Rao, Gorrepati Naveena, Narayanam Acharyulu P.S., Rambabu K. and
Potluri Haritha
Res. J. Chem. Environ.; Vol. 29(4); 26-38;
doi: https://doi.org/10.25303/294rjce026038; (2025)
Abstract
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.
