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.

Synthesis and identification of two potential oxidation degradants of oxymetazoline.

Two potential oxidation degradants of oxymetazoline have been isolated by liquid chromatography and monitored by electrospray single quadrupole mass spectrometry. The structures of the products are shown to be oxymetazoline N-oxide and hydroxyamine by multiple-stage fragmentation ion trap mass spectrometry. The product ion spectra were installed in a library database and the library was used to examine an aged commercial product; one of the degradants was detected, but at a level of less than 0.