Analysis of whole blood samples using triple quadrupole inductivity coupled plasma mass spectrometry (ICP-MS)

Importance of the topic

Accurate measurement of essential and toxic elements in whole blood is critical for clinical research, occupational health screening and forensic toxicology. Trace and major element profiles inform disease risk, environmental exposure and nutritional status. High-throughput, robust multi-element analysis enables large-scale studies and reliable monitoring of population health.

Objectives and study overview

This work aimed to develop and validate a simple, fast and robust analytical method for simultaneous determination of major, essential and toxic elements in whole blood using triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS). The study evaluated sensitivity, precision, linearity and long-term robustness for routine high-throughput analysis.

Methodology

Sample preparation involved 50× dilution of whole blood with a matrix containing Triton X-100, NH4OH, EDTA and HNO3. Internal standards and gold were added to stabilize mercury and monitor recovery. Two collision/reaction cell modes were employed: helium kinetic energy discrimination (He KED) for normal-mass analytes and TQ-O2 mass-shift mode for elements prone to spectral interferences.

Instrumentation

Thermo Scientific iCAP MTX ICP-MS coupled to an iSC-65 autosampler with “Step Ahead” feature.

• Nebulizer: PFA concentric, 400 µL/min
• Collision cell gases: He (4.2 mL/min) for KED, O2 (0.32 mL/min) for TQ-O2
• Interface: nickel sampler and skimmer cones
• Operating power: 1,550 W
• Acquisition: 0.1 s dwell, 5 sweeps, 3 main runs; total sample time 3 min 14 s

Main results and discussion

Detection limits (MDLs) for 43 elements ranged from sub-ng/L to several µg/L after dilution, with calibration curves showing R2 > 0.9995 across 8 orders of magnitude. Use of TQ-O2 effectively removed oxide and isobaric interferences for As, Se, Ti, V and others, while He KED preserved sensitivity for low-mass analytes like Li and Be.
The method was applied to three WHO-certified reference whole blood materials at low, medium and high levels. Measured concentrations agreed within 5–10 % of certified values. A long-term robustness test of 287 injections over ~15 h showed consistent internal standard recoveries (75–112 %) and no cone fouling.
Analysis of human, horse and pig blood highlighted distinct major element profiles, demonstrating the method’s applicability to diverse biological matrices.

Benefits and practical applications

• High throughput: ~180 samples plus QC in a single 15 h sequence
• Broad elemental coverage: Li to U in one run
• Low detection limits ideal for trace toxicants
• Minimal maintenance: no cone deposition after >1,000 samples
• Step Ahead autosampler reduced total analysis time by 9 %

Future trends and potential applications

Integration of automated sample preparation and AI-driven data analysis could further increase laboratory throughput and data quality. Expansion of reaction gas chemistries, miniaturized field-deployable ICP-MS units, and coupling with separation techniques (HPLC-ICP-MS) will broaden applications in pharmacology, environmental biomonitoring and personalized medicine.

Conclusion

The combined use of He KED and TQ-O2 on a triple quadrupole ICP-MS platform delivers a robust, sensitive and accurate multi-element method for whole blood analysis. The approach meets rigorous detection limits, linearity and long-term stability requirements, supporting high-throughput workflows in clinical and environmental research.

Reference

Seronorm Trace Elements in Whole Blood L-1, L-2 and L-3 Certified Reference Materials, SERO, Norway