¹H and ¹³C NMR Assignment of Sunitinib Malate in Aqueous Media

Despite expanding therapeutic application of sunitinib and advances in its formulation, pharmacochemical and spectroscopical study on its aqueous solution is rather insufficient due to poor solubility of its base or salt form. In this report, ¹H (900 MHz) and ¹³C (225 MHz) NMR spectra of sunitinib malate in H₂O/D₂O=9/1 have been analyzed, whose spectral peaks have been assigned to each hydrogen and carbon atom, assisted by a combination of two-dimensional homo- and heteronuclear NMR: COSY, HSQC-DEPT, and HMBC. The assignment of labile H-N hydrogens in ¹H NMR spectrum is of particular interest in aqueous media, where such labile hydrogens could be potentially affected by intermolecular interactions (e.g., hydrogen bonding) with co-solvated constituents. Peak splitting patterns and corresponding ⁿJ(H-H), ⁿJ(H-F), and ⁿJ(C-F) coupling constants observed in each assigned spectrum have been jointly discussed, and ⁿJ(C-F) coupling constants were compared to those taken in DMSO-d6.