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.

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.

Ultra high performance liquid chromatography-time-of-flight high resolution mass spectrometry in the analysis of hexabromocyclododecane diastereomers: method development and comparative evaluation versus ultra high performance liquid chromatography coupled to Orbitrap high resolution mass spectrometry and triple quadrupole tandem mass spectrometry.

An efficient ultra high performance liquid chromatography (UHPLC)-time-of-flight high resolution mass spectrometry (TOF-HRMS) method was elaborated for the determination of hexabromocyclododecane (HBCD) diastereomers in fish samples and compared against UHPLC-Orbitrap-HRMS and UHPLC-triple quadrupole (QqQ) tandem MS (MS/MS) techniques. The TOF-HRMS analyzer was operated at high resolution (>10000 full width at half maximum (FWHM)) with scanning the m/z range from 600 to 700, to achieve picogram quantitation limits. The effects of various operational parameters on the instrumental response were systematically investigated. Evaluation of the influence of sample clean-up procedure steps on signal suppression effect including removal of the matrix components by means of destructive acidic treatment or non-destructive gel permeation chromatography (GPC), and additional Florisil column chromatography step showed that the analytical response of UHPLC-TOF-HRMS system is much more affected by the presence of matrix components in the final extracts in comparison with UHPLC-Orbitrap-HRMS and UHPLC-QqQ-MS/MS systems. The method was robustly validated and used for the analysis of eel (Anquilla anquilla) samples originating from a Latvian lake. UHPLC-TOF-HRMS showed a suitable performance under the optimized conditions: recoveries for three selected diastereomers in the range of 99-116%; repeatability and intermediate precision expressed as relative standard deviation (RSD) in the ranges of 2.3-7.1% and 2.9-8.1%, respectively. The elaborated method achieved instrumental limits of quantification (i-LOQ) of 0.9-4.5pg on column that were suitable for the trace analysis of three HBCD diastereomers, corresponding to the method limits of quantification (m-LOQ) of 7.0-29pgg(-1) wet weight (w.w.). The efficiency of UHPLC-TOF-HRMS method was evaluated by comparing the performance characteristics and analytical data from real samples with the validation data and real sample results obtained by applying UHPLC-Orbitrap-HRMS and UHPLC-QqQ-MS/MS techniques for the analysis of HBCD in the same fish samples. Statistical assessment of the experimental data by means of the Fiedman's test revealed that UHPLC-TOF-HRMS, UHPLC-QqQ-MS/MS and UHPLC-Orbitrap-HRMS techniques produced adequate and similar results regarding the HBCD content in fish samples. The presence of HBCD diastereomers was confirmed in all the analyzed eels at concentrations up to 554pgg(-1) w.w. for total HBCD and a diastereomer pattern typical for aquatic biota was observed with strong predominance of α-HBCD. The UHPLC-TOF-HRMS is an appropriate technique for diastereomer-specific quantification of HBCD content in fish samples.