Tracing the anticancer compound [Ru II (η 6 -p-cymene)(8-oxyquinolinato)Cl] in a biological environment by mass spectrometric methods.

Ruthenium-based complexes have attracted attention as promising anticancer candidates due to their lower general toxicity than the widely used platinum drugs. The complex [Ru ^II (η ⁶ -p-cymene)(8-oxyquinolinato)Cl] 1 has shown significant cytotoxic activity in cancer cells, independent of the cellular uptake. In an attempt to rationalize this finding, we investigated the fate of 1 in cells as well as developed an analysis method for 1 and its derivatives based on molecular mass spectrometry. The methods were applied for the analysis of cell medium and HCT116 human colorectal cancer cell lysate samples. The amount of Ru detected in cell lysate after treatment with 1 by ICP-MS was virtually time-independent, while the Ru content in the cell pellet increased significantly over the course of 24 h. The compound was still detectable by LC-ESI-TOF-MS after 24 h in cell lysate as its [1- Cl] ⁺ ion that may be formed directly from 1 or after a chlorido-aqua ligand exchange reaction facilitated in the cytosol.