The potential advantage of
platinum(iv) complexes as alternatives to classical
platinum(ii)-based drugs relies on their kinetic stability in the body before reaching the
tumor site and on their activation by reduction inside
cancer cells. In this study, an analytical workflow has been developed to investigate the reductive biotransformation and kinetic inertness of
platinum(iv)
prodrugs comprising different
ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of
platinum(iv) complexes in blood pellets and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion. An analytical approach based on reversed-phase (RP)-ICP-MS was used to monitor the parent compound and the formation of metabolites using two different extraction procedures. The
ligand coordination sphere of the
platinum(iv) complexes had a significant impact on their accumulation in red blood cells and on their degree of kinetic inertness in whole human blood. The most lipophilic
platinum(iv) compound featuring equatorial chlorido
ligands showed a pronounced penetration into blood cells and a rapid reductive biotransformation. In contrast, the more hydrophilic
platinum(iv) complexes with a
carboplatin- and
oxaliplatin-core exerted kinetic inertness on a pharmacologically relevant time scale with notable amounts of the compound accumulated in the plasma fraction.