Capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry: A novel approach for the analysis of anticancer metallodrugs in human serum and plasma

The development of metal-based chemotherapeutics lacks methods which are capable of providing early indication on the potential of new metal complexes as future anticancer drugs. Since most of these compounds are administered intravenously, serum proteins are the first available biological binding partners in the bloodstream. For platinum-based anticancer drugs the interaction with serum proteins is regarded as an important contribution to the side effects accompanying chemotherapy. In contrast, newly developed ruthenium compounds are thought to be transported into the tumor in a protein-bound form. In here, the application of CE hyphenated to inductively coupled plasma (ICP)-MS, applying Polybrene-coated capillaries, is demonstrated for studying the interaction of indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) with HSA and transferrin, which are important transport proteins. Furthermore, the applicability of the method to human serum and plasma and, more importantly, to real-world patient samples was proven. KP1019 was found to bind to a high degree to HSA both in serum, plasma and the patient samples. Only minor fractions of ruthenium were found attached to other proteins.