Chemical degradation of platinum oncolytics in urine and speciation of the inorganic contaminants cisplatin and carboplatin relevant in waste water

Abstract

Understanding the prevalent form of platinum (Pt) based antineoplastic agents, used in chemotherapy, is of importance to develop a remediation strategy that restricts aquatic exposure. The speciation of Pt-based compounds was measured in actual patients’ urine using hydrophobic interaction liquid chromatography (HILIC) equipped with an ICP-MS detector. Carboplatin showed poor metabolization and intact excretion 11 h after administration, whereas cisplatin underwent a rapid aquation in the first 7 h. To compare, the in vitro degradation rate of cisplatin, carboplatin and oxaliplatin was determined in synthetic human urine, mimicking true environmental conditions. The fraction of intact molecules was measured at regular intervals following incubation at 37 °C, resulting in degradation rate constants. The chemical stability was highest for carboplatin (k = 0.0143 ± 0.0012 min−1), versus faster degradation of oxaliplatin and cisplatin by exponential decay with k1 of 0.0026 ± 0.0001 min−1 and k2 = 5.59 ± 0.46 × 10−6 min−1, respectively. These kinetic parameters can serve as input to further expand modelling databases and improve the predictive power of speciation software to estimate eco-toxicity risks. Considering the strong residual cytotoxicity of the platinum antineoplastic molecules following renal clearance and human excretion, the contaminants are of high environmental concern and offer potential for metal recovery using advanced treatment steps. In such water treatment processes, especially carboplatin, above all cancerostatic platinum compounds, should be addressed since it is more persistent in the aquatic environment.

Keywords

• Pharmaceuticals
• Inorganic contaminants
• Speciation analysis
• Ecotoxicity