FI-ICP-TOFMS for quantification of biologically essential trace elements in cerebrospinal fluid – high-throughput at low sample volume

In this work, we introduce a high-throughput quantitative multi-element method for biological fluids enabled by omitting sample preparation and an analysis time of a few seconds per sample. For the first time, flow injection of an undiluted cerebrospinal fluid (CSF) was combined to state-of-the-art ICP-TOFMS detection for multi-element analysis. Owing to the low sample volume and trace element concentrations of the CSF, flow injection methods with only 5 μL sample intake were used in combination with an icpTOF 2R TOF-based ICP-MS instrument. Due to the lack of certified reference materials for CSF analysis, a validated method employing open vessel digestion of the CSF material in combination with ICP-sectorfield-MS analysis was carried out and used as a reference. Additionally, the performance of the flow injection ICP-TOFMS was cross-validated by flow injection quadrupole-based ICP-MS/MS analysis using both external calibration and isotope dilution strategies. In the latter case, the sample had to be injected several times because of the need for tailored gas conditions for different elements. Overall, flow injection of biological fluids delivered quantitative values, which were in excellent agreement with the gold standard established by ICP-SFMS demonstrating the capability of ICP-TOFMS analysis in terms of resolution and sensitivity for the accurate quantification of trace elements in biological samples

Critical assessment of different methods for quantitative measurement of metallodrug-protein associations

Quantitative screening for potential drug–protein binding is an essential step in developing novel metal-based anticancer drugs. ICP–MS approaches are at the core of this task; however, many applications lack in the capability of large-scale high-throughput screenings and proper validation. In this work, we critically discuss the analytical figures of merit and the potential method-based quantitative differences applying four different ICP–MS strategies to ex vivo drug–serum incubations. Two candidate drugs, more specifically, two Pt(IV) complexes with known differences of binding affinity towards serum proteins were selected. The study integrated centrifugal ultrafiltration followed by flow injection analysis, turbulent flow chromatography (TFC), and size exclusion chromatography (SEC), all combined with inductively coupled plasma-mass spectrometry (ICP–MS). As a novelty, for the first time, UHPLC SEC-ICP–MS was implemented to enable rapid protein separation to be performed within a few minutes at > 90% column recovery for protein adducts and small molecules.© The Author(s) 201