Liquid chromatography and mass spectrometric studies of gilteritinib fumarate and characterization of its major degradation products by NMR

Abstract

Gilteritinib fumarate (GTB) is an anti-cancer drug belonging to the class of tyrosine kinase inhibitors used for the treatment of acute myeloid leukemia. It has been designated as an orphan drug by the US Food and Drug Administration (US FDA). The present research focused on carrying out the forced degradation studies of GTB and developing a UHPLC-PDA stability indicating method capable of separating GTB and its degradation products. The degradation studies were carried out under hydrolytic (acid, base, and neutral), oxidative, thermal, and light conditions. The drug degraded under hydrolytic and oxidative conditions whereas it was found to be stable under thermal and light exposure. The separation of the components was achieved on an Acquity BEH C18 column (2.1 × 100 mm; 1.7μ) and a mobile phase comprising ammonium acetate and acetonitrile eluting in gradient mode at a flow rate of 0.3 mL min⁻¹. A total of five degradation products were obtained and were structurally characterized with the help of accurate mass and tandem mass experiments performed on LC-QTOF-MS equipment and DP-1 was isolated and characterized using 1D and 2D NMR experiments. The UHPLC-PDA method was validated as per the ICH Q2 (R1) guidelines for its accuracy, precision, linearity, and specificity. The method was found to be appropriate for its intended purpose and can be effectively used in the determination of GTB and its degradation products and/or impurities in bulk drugs as well as formulations.