Speciation of cancerostatic Pt compounds in the environment

The proposed project focuses on the development of analytical methods for identification and quantification of cancerostatic platinum compounds (CPC) and their metabolites in human excretions, in hospital effluents and in surface water. Nowadays the use of CPC has gained undisputed importance in the chemotherapy of several types of cancer. Consequently, CPC are continuously spread into the environment with excretion into wastewater being the major source. The active substances and their metabolites are expected to pass through municipal sewage treatment plants, reaching surface and ground waters. Biotransformation processes, mobility and fate of these compounds in the aquatic environment have not been studied so far, even though their toxicity (carcinogenic, mutagenic, fetotoxic) is well demonstrated. The metabolism of these substances has to be investigated in different aquatic media, in order to support future studies, which aim at the assessment of health risks and environmental impact. New analytical approaches will be applied to samples representing different stages of the water cycle in order to study biotransformation, degradation and adsorption processes. Highly sensitive and specific miniaturized high performance liquid chromatography - inductively coupled sector field mass spectrometry (HPLC-ICP-SFMS) will be applied for solving this challenging analytical problem. As complementary detection method electrospray mass spectrometry will be employed. The new findings will give first indications for the state of CPC in the aquatic environment. Furthermore the obtained results will be the base for the development of new strategies for elimination of the substances from hospital effluents.

Cancerostatic platinum compounds (CPC) represent an important class of antineoplastic drugs, which are widely used in the chemotherapy of lung, cervical, testicular, head and neck, bladder, and ovarian cancer. The three CPC currently approved in Europe are cisplatin, carboplatin and oxaliplatin. After chemotherapy considerable portions of the drugs are excreted reaching hospital wastewater. Since nowadays cancer treatment is frequently performed out-ward, another important fraction of CPC is directly released into communal waste water. It is undisputed that CPC are essential for anti-cancer therapy. However, the environmental impact of the drugs has to be assessed, since the International Agency for Research on Cancer includes cisplatin in group 2A (probably cancerogenic to humans). As a matter of fact the toxicity of a substance is strongly related to its chemical structure (species), and therefore the presented project aimed at the development of analytical methods for speciation of CPC in aquatic samples. In a second step these methods were applied to investigate CPC chemistry (biotransformation and degradation processes) in human excretions and at different stages of the water cycle. Employing highly sophisticated speciation methods the first research within the project concerned model studies of CPC stability under surface water and waste water conditions. It was found that carboplatin and oxaliplatin are stable to a high degree in both media; whereas 50 % of the initial amount of cisplatin was rapidly (24 h) hydrolyzed yielding the degradation compounds mono- and diaquacisplatin. In a consecutive project step the abundance of platinum containing compounds in the urine of cancer-patients treated with CPC was investigated. The measurements revealed that the urine of patients treated with cisplatin contains similar amounts of the intact drug and monoaquacisplatin. Patients treated with carboplatin excreted mainly the intact drug without significant portions of degradation compounds. For oxaliplatin it could be shown that the drug undergoes intensive biotransformation leading to a complete decay of the parent drug and the presence of a variety of platinum containing products in patient urine. This data was the base of the last part of the project aiming at the investigation of the behaviour of CPC during waste water treatment. An input-output budget was established via the measurement of waste water from the oncologic ward of the Vienna University Hospital. We found that approximately 30 % of the administered CPC are found in the hospital waste water, which implies that the patients emit the remaining fraction into communal waste water after their check-out. Measurement at a pilot membrane bioreactor system situated in the Vienna University Hospital revealed that cisplatin, monoaquacisplatin and the oxaliplatin degradation products can be eliminated to a large extend by waste water treatment via adsorption to sewage sludge and suspended solids. However, it was found that a considerable fraction of carboplatin present in hospital waste water persists sewage treatment and enters the receiving water body.