Investigation of the reaction of cisplatin with methionine in aqueous media using HPLC-ICP-DRCMS

Abstract

The reaction of cisplatin with methionine was studied by high performance ion chromatography coupled to inductively coupled plasma mass spectrometry equipped with dynamic reaction cell technique (HPLC-ICP-DRCMS) at two different cisplatin concentrations simulating chemotherapy conditions and waste water levels. The reaction of cisplatin with methionine was monitored over a period of 16 h. Accurate quantification of all platinum containing compounds was achieved via species unspecific on-line isotope dilution mass spectrometry. A limit of detection (LOD) of 0.31, 0.25, 3.83, 1.07, 0.56, 0.82 and 2.38 µg L⁻¹ was calculated at m/z 194 for cisplatin, monoaquacisplatin, diaquacisplatin and the four platinum containing adducts, respectively. Stoichiometric platinum/sulfur ratios were assessed for characterization of the four adducts using ICP-DRCMS detection employing oxygen as reaction gas. An excellent sulfur detection limit of 1.30 µg L⁻¹ could be achieved by HPLC-ICP-DRCMS (20 µL injection volume). At high cisplatin levels (0.6 mmol L⁻¹) typical in chemotherapy, it was found that adducts show different kinetic behavior depending on the two investigated chloride levels (1.5 and 150 mmol L⁻¹). Moreover, the reaction course depended on the concentration of the reactants, i.e. cisplatin and methionine. Experiments simulating possible reactions of the compounds in the aquatic environment revealed that at low µmol L⁻¹ levels no adduct formation occurred. Finally, the stability of the four adducts potentially formed during chemotherapy was investigated representing the dilution of patient urine via hospital waste water. A considerable amount of highly active monoaquacisplatin was formed, indicating a reversal of detoxification reaction pathways of the human body.