Tandem mass spectrometry characterization of a conjugate between oleuropein and hydrated cis-diammineplatinum (II).

RATIONALE: Oleuropein (Ole) has been claimed to mitigate cisplatin (CP) induced acute injury in kidney and liver of mice. In-vitro reactivity of hydrated CP species with Ole, and Ole metabolite hydroxytyrosol (HT) is of great interest as the preliminary step for gathering in-vivo information on the possible physiological role of the Ole/HT-cis-diammineplatinum (II) (Ole/HT-cis-DAP) conjugate.

METHODS: Reversed-phase liquid chromatography coupled to electrospray ionization and mass spectrometry using a linear-ion trap instrument (RPLC-ESI-MS) and tandem mass (MS/MS) measurements, both in positive and negative ion mode, revealed the molecular identity of platinum-based conjugates.

RESULTS: The Ole-cis-DAP conjugate (i.e., C25 H36 N2 O13 PtII ) features two cis-ammine non-leaving ligands and a bidentate catechol ligand moiety belonging to Ole; the coordination of the central Pt (II) is square-planar with non-equivalent bond angles compared with the ideal arrangement of 90°. HT, the free Ole metabolite excreted in human urine, acts as bidentate O,O-donor ligand of cis-DAP as well.

CONCLUSIONS: The first evidence, together with structural information, is provided about the in-vitro formation of a conjugate between cis-DAP and Ole or its urinary metabolite HT. Presuming that such conjugates are also generated in-vivo, the mechanisms by which they might contribute to reduce CP toxicity remain to be elucidated.