Evaluation of the accumulation of disulfiram and its copper complex in A549 cells using mass spectrometry.

The famous alcohol-aversion drug disulfiram (DSF) is a promising candidate for repurposing in cancer therapy, as indicated by many ongoing and completed clinical trials. Existing researches focus on demonstrating that the anti-cancer activity of DSF is enhanced by copper ions, or solving the problem that DSF is easily decomposed in the body to lose its activity. However, the metabolic kinetics of its ultimate anti-cancer metabolite DDC-Cu (bis-diethyldithiocarbamate-copper) in cells and how it exerts anti-cancer mechanisms remain unclear. In this work, mass spectrometric evaluation of the intracellular and extracellular accumulation of DSF and its copper complex DDC-Cu was performed. Combined with cytotoxicity assay, staining analysis and flow cytometry, we found that DDC-Cu could easily pass through the cell membrane of A549 cells, and accumulate intracellularly for a long time. This process can lead to cellular morphological changes, an increase in ROS content, cell cycle arrest in the G0/G1 phase and apoptosis. Besides, molecular cancer-relevant targets of DDC-Cu in cancer cells were further discussed. This work investigated the cytotoxic mechanism of DDC-Cu, which has important clinical significance for its application in cancer therapy.

Analysis of trace metals in water samples using NOBIAS chelate resins by HPLC and ICP-MS.

The pre-concentration of major constituents is crucial to accurate and precise determination of trace metals in water samples by inductively coupled plasma mass spectrometry (ICP-MS). In this work, NOBIAS chelate resins were used in the sample concentration for both HPLC and ICP-MS detection. 4-(2-Pyridylazo) resorcinol (PAR) was selected as a precolumn chelating reagent for this research. 520 nm wavelength was used as to minimize the peak of PAR and to reduce baseline noise for HPLC analysis. The sample pre-treatment step was achieved by enrichment and Cd(II), Co(II), Cu(II), Mn(II), Ni(IV), Pb(II), and Zn(II) were detected in the bottled water and tap water samples. The results of two detection methods of ICP-MS and HPLC were compared. Results showed that by acquiring 50-time pre-concentrates of test samples using 250 mg of the Nobias-chelate PA1 chelating resin, the metal contents could be accurately detected using both ICP-MS and HPLC. And the approach of HPLC enables the quantitative detection of bottled water and tap water at different concentrations with determination coefficient (R2) greater than 0.9990. This simple and cost-effective quantitative detection approach using NOBIAS chelate resins and HPLC may widen the application of NOBIAS chelate resins for quantitative detection of more water samples.