Occupational exposure to platinum drugs during intraperitoneal chemotherapy. Biomonitoring and surface contamination.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced over the last decade for the treatment of peritoneal carcinomatosis. In this procedure, heated cytotoxic drugs are administered directly into the abdominal cavity, ensuring cancer cells to be exposed while reducing systemic toxicity. More recently, pressurized intraperitoneal aerosol chemotherapy (PIPAC), where the chemotherapeutic drug is injected into the peritoneal cavity as an aerosol under pressure, has been proposed to patients in palliative situation, as a new approach. The amount of drug used is up to 10 fold lower than in HIPEC. The use of cytotoxic drugs poses an occupational risk for the operating room personnel. This study investigated the potential exposure of the medical staff by biomonitoring and surface contamination measurements, during a HIPEC procedure and a PIPAC procedure. METHOD: Wipe samples were collected from various locations in operating rooms including gloves, hands, devices and floor. Urines samples were collected from 10 volunteers of the medical staff and from a control group. The platinum analysis was performed by inductively coupled plasma mass spectrometry. RESULTS: Significant contaminations were observed on the floor, gloves, shoes and devices. However, urinary platinum was below the limit of quantification (<10 ng/L) for more than 50% of samples from the healthcare workers performing HIPEC and PIPAC. Concentrations did not differ significantly from those reported for the control group. CONCLUSION: There appears to be little risk of exposure to platinum drugs during HIPEC and PIPAC providing the adequate safety measures are implemented.

Can neutral analytes be concentrated by transient isotachophoresis in micellar electrokinetic chromatography and how much?

Transient isotachophoresis (tITP) is a versatile sample preconcentration technique that uses ITP to focus electrically charged analytes at the initial stage of CE analysis. However, according to the ruling principle of tITP, uncharged analytes are beyond its capacity while being separated and detected by micellar electrokinetic chromatography (MEKC). On the other hand, when these are charged micelles that undergo the tITP focusing, one can anticipate the concentration effect, resulting from the formation of transient micellar stack at moving sample/background electrolyte (BGE) boundary, which increasingly accumulates the analytes. This work expands the enrichment potential of tITP for MEKC by demonstrating the quantitative analysis of uncharged metal-based drugs from highly saline samples and introducing to the BGE solution anionic surfactants and buffer (terminating) co-ions of different mobility and concentration to optimize performance. Metallodrugs of assorted lipophilicity were chosen so as to explore whether their varying affinity toward micelles plays the role. In addition to altering the sample and BGE composition, optimization of the detection capability was achieved due to fine-tuning operational variables such as sample volume, separation voltage and pressure, etc. The results of optimization trials shed light on the mechanism of micellar tITP and render effective determination of selected drugs in human urine, with practical limits of detection using conventional UV detector.

Flow injection analysis with electrochemical detection for rapid identification of platinum-based cytostatics and platinum chlorides in water.

Platinum-based cytostatics, such as cisplatin, carboplatin or oxaliplatin are widely used agents in the treatment of various types of tumors. Large amounts of these drugs are excreted through the urine of patients into wastewaters in unmetabolised forms. This phenomenon leads to increased amounts of platinum ions in the water environment. The impacts of these pollutants on the water ecosystem are not sufficiently investigated as well as their content in water sources. In order to facilitate the detection of various types of platinum, we have developed a new, rapid, screening flow injection analysis method with electrochemical detection (FIA-ED). Our method, based on monitoring of the changes in electrochemical behavior of analytes, maintained by various pH buffers (Britton-Robinson and phosphate buffer) and potential changes (1,000, 1,100 and 1,200 mV) offers rapid and cheap selective determination of platinum-based cytostatics and platinum chlorides, which can also be present as contaminants in water environments.

Novel separation method for highly sensitive speciation of cancerostatic platinum compounds by HPLC-ICP-MS.

A high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) method is presented for analysis of cisplatin, monoaquacisplatin, diaquacisplatin, carboplatin, and oxaliplatin in biological and environmental samples. Chromatographic separation was achieved on pentafluorophenylpropyl-functionalized silica gel. For cisplatin, carboplatin, and oxaliplatin limits of detection of 0.09, 0.10, and 0.15 microg L(-1), respectively, were calculated at m/z 194, using aqueous standard solutions. (3 microL injection volume). The method was utilized for model experiments studying the stability of carboplatin and oxaliplatin at different chloride concentrations simulating wastewater and surface water conditions. It was found that a high fraction of carboplatin is stable in ultrapure water and in solutions containing 1.5 mol L(-1) Cl-, whereas oxaliplatin degradation was increased by increasing the chloride concentration. In order to support the assessment of oxaliplatin eco-toxicology, the method was tested for speciation of patient urine. The urine sample contained more than 17 different reaction products, which demonstrates the extensive biotransformation of the compound. In a second step of the study the method was successfully evaluated for monitoring cancerostatic platinum compounds in hospital waste water.