The chemistry of multi-protic drugs Part 1: a potentiometric, multi-wavelength UV and NMR pH titrimetric study of the micro-speciation of SKI-606.

The application of a combination of potentiometric, spectrophotometric and nuclear magnetic resonance (NMR) pH titrimetric methodology to measure the macroscopic and to calculate the microscopic protonation constants of SKI-606, a multi-protic compound is described. This compound is currently under evaluation as a candidate drug for the treatment of cancer. SKI-606 was found to have four protonatable sites in the pH range 1-12.