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Single cell - tandem ICP-mass spectrometry (SC-ICP-MS/MS) was used for the determination of the absolute amount of Pt (coming from exposure to various concentration levels of cisplatin as a chemotherapeutic drug) and five endogenous elements (P, S, Fe, Cu and Zn) in individual human cells of three different types - Raji, Jurkat and Y79. Optimum conditions were obtained by using a sample introduction unit transporting cell suspension containing approx. 5 × 10 4  cells per mL at a flow rate of 10 μL min -1 to a nebulizer with narrow internal diameter (250 μm i.d.), mounted onto a total consumption spray chamber. Interference-free conditions were obtained in tandem MS mode (i) for P and S by pressurizing the collision/reaction cell (CRC) with O 2 and monitoring the PO + and SO  +  reaction product ions and (ii) for Fe by pressurizing the CRC with NH 3 and monitoring the Fe(NH 3 ) 2 + reaction product ion. The quantification approach was validated by comparison of the absolute amounts of the target elements (in fg per cell) as obtained using SC-ICP-MS/MS with those obtained after acid digestion of approx. 2 × 10 6  cells and subsequent solution ICP-MS/MS analysis ("bulk" analysis). A higher Pt cell content was observed upon increasing the concentration of the cisplatin solution the cells were exposed to during 24 h. The Pt mass per cell (fg) increased linearly as a function of the cisplatin concentration, but a higher Pt uptake was found in the case of Jurkat cells compared to the other cell types. A cell viability assay showed a lack of chemosensitivity to cisplatin below 200 μM for the Raji and Y79 cell line, but an IC 50 value of 11.1 ± 1.3 μM for Jurkat cells. This difference in chemo-responsiveness between the different cell types supported the difference in Pt uptake as indicated via SC-ICP-MS analysis. The increasing level of Pt did not have a marked effect on the contents of the endogenous elements monitored in Raji and Y79 cells, but a decrease in the P and S cell content upon increasing cisplatin treatment was observed for Jurkat cells. This can most likely be attributed to stress induced by the chemotherapeutic treatment in cells showing chemosensitivity towards cisplatin. The results also indicate differences in the absolute amount of endogenous element per cell between different cell types, suggesting the potential of SC-ICP-MS as a "metallo-fingerprinting" tool., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The devices used – the MVX-7100 μL sample introduction unit, the single-cell glassware and the AT8900 ICP-MS/MS instrument – were made available by Teledyne Cetac Technologies, Glass Expansion and Agilent Technologies, respectively., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This paper reports on an evaluation of the suitability of a novel sample collection approach, volumetric absorptive micro-sampling (VAMS), in the context of the determination of ultra-trace concentrations of prosthesis-related metals (Al, Ti, V, Co, Cr, Ni, Sr and Zr) in whole blood. In a first phase, a simple dilute-and-shoot approach (100-fold dilution) followed by tandem ICP - mass spectrometry (ICP-MS/MS) analysis was developed for the accurate and sensitive determination of the target elements. The ICP-MS/MS method relies on the use of mass shift reactions proceeding when pressurizing the collision/reaction cell (CRC) with CH 3 F/He for dealing with spectral overlap. Limits of detection (LoDs) between 0.3 and 30 ng L -1 were attained in a multi-element approach. The accuracy of the method was demonstrated via successful analysis of the reference materials Seronorm Whole Blood Levels 1 and 3, and real venous blood samples, spiked with the target elements at different concentration levels (5-50 μg L -1 ). Although the implementation of VAMS devices introduced contamination problems for Al, Cr and Ni, VAMS followed by ICP-MS/MS analysis shows potential for future real-life routine applications when assessing levels of Ti, V, Co, Sr and/or Zr., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A fast, accurate and precise method for the separation and determination of the total contents of drug-related Cl and Br in human blood plasma, based on high performance liquid chromatography - inductively coupled plasma - tandem mass spectrometry (HPLC-ICP-MS/MS), has been developed. The novel approach was proved to be a suitable alternative to the presently used standard methodology (i.e. based on a radiolabelled version of the drug molecule and radiodetection), while eliminating the disadvantages of the latter. Interference-free determination of (35)Cl has been accomplished via ICP-MS/MS using H2 as reaction gas and monitoring the (35)ClH2(+) reaction product at mass-to-charge ratio of 37. Br could be measured "on mass" at a mass-to-charge of 79. HPLC was relied on for the separation of the drug-related entities from the substantial amount of inorganic Cl. The method developed was found to be sufficiently precise (repeatability <10% RSD) and accurate (recovery between 95 and 105%) and shows a linear dynamic range (R(2)>0.990) from the limit of quantification (0.05 and 0.01 mg/L for Cl and Br in blood plasma, respectively) to at least 5 and 1mg/L for Cl and Br, respectively. Quantification via either external or internal standard calibration provides reliable results for both elements. As a proof-of-concept, human blood plasma samples from a clinical study involving a newly developed Cl- and Br-containing active pharmaceutical ingredient were analysed and the total drug exposure was successfully described. Cross-validation was achieved by comparing the results obtained on Cl- and on Br-basis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Methyl fluoride (a mixture of 10% CH3F and 90% of He) was evaluated as a reaction gas in inductively coupled plasma-tandem mass spectrometry (ICPMS/MS) in the context of the determination of ultratrace concentrations of medically relevant metals (Al, Co, Cr, Mn, Ni, Ti, and V) in blood serum and urine. Via product ion scanning, whereby only ions of the mass-to-charge ratio of the target nuclide were admitted into the octopole reaction cell, the various reaction product ions formed for each of the target elements were identified at different CH3F gas flow rates. Limits of detection (LODs) and of quantification (LOQs) and linearity of the calibration curve were documented under (i) optimized ICPMS/MS conditions for single-element monitoring and (ii) compromise conditions, allowing for multielement determination. Even under compromise settings, instrumental LODs were below 10 ng/L for all target elements, while the use of CH3F provided interference-free conditions for their determination in the biofluids of interest. Quantitative data obtained for Seronorm blood serum and urine reference materials were in excellent agreement with the corresponding reference values and/or results obtained using double-focusing sector-field ICPMS (for those elements for which no certified values were available or that were affected during reconstitution), proving the potential of this reaction gas for multielement ultratrace analysis via ICPMS/MS.