Determination of Cisplatin in Human Blood Plasma and Urine Using Liquid Chromatography-Mass Spectrometry for Oncological Patients With a Variety of Fatty Tissue Mass for Prediction of Toxicity

Abstract

Aim: The research was aimed to analyze a level of triglycerides in blood serum as a possible new marker of toxicity, particularly in patients with excess body weight, receiving cisplatin. Materials and Methods: Study involved 20 oncological patients with stage III lung cancer, who received palliative treatment with cisplatin. High-performance liquid chromatography was used for quantitative determination of pure cisplatin in urine and blood samples. Cisplatin concentration of the test samples was determined based on the data obtained from the calibration graph. Results: Quantitative determination of pure cisplatin is quite complicated. The elimination half-time for one of the groups was observed higher almost by half than for other patients. Higher dose of cisplatin showed a significant association with increase in triglyceride levels. We found a close correlation between body mass index and triglyceride changes during chemotherapy (p = 0.001; r = 0.67). The results indicate that a higher body mass index gives higher fluctuations of triglyceride levels in blood serum. Analyses of correlation between level of triglycerides and elimination half-time show that by an increase in the level of triglycerides in the blood serum cisplatin elimination half-time is prolonged (R2 Linear = 0.596). Cisplatin concentration in urine is higher and elimination takes longer time at elevated levels of triglycerides, where close correlation between fraction of excreted substance in urine and concentration parameters was seen (p < 0.01). Also good correlation for body mass index with fraction of excreted substance in urine and concentration parameters was observed (p < 0.05). Conclusion: Clearance of cisplatin, which was determined by the chromatographic method, is reduced in individuals with increased adipose tissue mass. Research data suggest that overweight affects cisplatin elimination from the body. The greater body fat mass can contribute to a greater rise of triglyceride level in blood serum. Triglycerides in blood plasma may serve as an additional indicator of higher cisplatin toxicity as a cardiotoxicity marker.

Mapping cisplatin-induced viscosity alterations in cancer cells using molecular rotor and fluorescence lifetime imaging microscopy

“…22,23,49 The choice of the drug dose in our study was based on the MTT-assay and a prior knowledge of concentration of cisplatin in the blood plasma of patients, which is 3 to 6 μM. 40,51 Previously, we showed that cisplatin at a concentration of 2.4 to 2.6 μM affects the proliferative ability rather than viability of cancer cells HeLa-the number of dead cells did not exceed 10%, whereas the cells growth was inhibited after 24 h exposure to cisplatin. 38 It is known that cisplatin increases the duration of S-phase and blocks cells in G2-phase of the cell cycle.…”

“…The tested concentrations of cisplatin were in the range of maximum concentrations of the drug in the blood plasma of patients, 1 to or 3 to on average. 40 The cells were incubated with the drug from 10 min to 48 h, spheroids—from 3 to 48 h, and viscosity was measured immediately after the treatment. Untreated cells or spheroids served as a control.…”

Anticancer Potential of Cinnamon Bark Extract (Cinnamomum burmanii) with Cisplatin Combination against P-glycoprotein and Apoptotic Influx Biomarkers

“…The higher the percentage of p-glycoprotein, the higher the cell's ability to resist the response of the given cytotoxic compound. In other words, if a low percentage of p-glycoprotein is found, then the cytotoxic ability of the drug has a positive effect on cells [11], [12], [13], [14], [15].…”

“…The p-glycoprotein substrate efflux is related to the energy consumption of ATP binding to NBD and hydrolysis. After ATP binding, ATP hydrolysis is essential for the conformational change of the p-glycoprotein from the outside to the inside that will continue the next efflux cycle [8], [9], [11], [15], [16]. This indicates that the combination of cinnamon bark extract of 68.73 ug/ ml and cisplatin of 117.5 uM has the best effect on drug efflux so that it has the potential to prevent cisplatin resistance.…”

Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples

“…More recently, some LC methods using tandem mass spectrometry (MS/MS) determination have been developed to analyze carboplatin in plasma [ 20 ], carboplatin and oxaliplatin in surfaces [ 21 ] and cisplatin, carboplatin, and oxaliplatin in surfaces employing zwitterionic hydrophilic interaction liquid chromatography (HILIC) [ 22 ]. There are also studies that have proposed the determination of cisplatin or carboplatin indirectly through derivatization with diethyldithiocarbamate DDTC in plasma and urine [ 2 , 23 , 24 , 25 ]. Therefore, the aim of this study was to propose an analytical method for the simultaneous determination of cisplatin, carboplatin, and oxaliplatin in human urine.…”