Total elemental analysis in clinical research using the Thermo Scientific iCAP TQ ICP-MS

Significance of the Topic

Trace elemental analysis in biological samples underpins clinical research and forensic toxicology, offering critical insights into the behavior of metals such as titanium in the human body. Investigating the degradation products of orthopedic and dental implants is particularly important in light of potential health risks. Robust, interference-free quantification of titanium at ultra-trace levels in fluids and tissues addresses an unmet analytical need.

Objectives and Study Overview

This work aimed to develop and validate a sensitive, accurate method for simultaneous multi-element determination—including titanium—in human serum reference materials and urine. Key goals included overcoming isobaric and polyatomic interferences, achieving low detection limits, and demonstrating long-term stability in a high-matrix clinical context.

Methodology and Instrumentation Used

Sample Preparation:

• Certified serum reference materials (Seronorm L-1, L-2) and human urine were gravimetrically diluted 1:10 in 0.5% HNO3/2% TMAH.
• Internal standards (Ge, Y, Rh, Te, Bi at 10 µg/L) were spiked into all samples and standards.
• Calibration range covered major (e.g., Ca, Mg, S) and minor (e.g., Sb, Cd, Ti) elements using multi-level standards and QC checks.

Instrumentation:

• Thermo Scientific iCAP TQ ICP-MS configured in triple quadrupole mode to enhance interference removal.
• Q1 rejects unwanted precursors; Q2 reaction cell uses NH3 or He to shift or attenuate interferences; Q3 isolates product ions.
• Analysis modes: SQ-KED for most elements (He collision, kinetic energy discrimination), SQ-NH3, and TQ-NH3 mass shift for titanium.
• Optimized parameters via Qtegra ISDS autotune: PFA nebulizer, cyclonic spray chamber at 3 °C, Ni cones, 1550 W RF power, tailored gas flows and bias voltages.

Main Results and Discussion

Titanium Quantification:

• TQ-NH3 mode yielded accurate Ti levels in Serum L-1 (6.64 µg/L) and L-2 (6.38 µg/L), matching certified ~6.8 µg/L; SQ modes overestimated due to interferences.
• Ammonia reaction formed [48Ti(NH3)3NH]+ at m/z 114, effectively removing Ca and polyatomic overlaps.

Multi-Element Performance:

• Excellent linearity (R² > 0.9998 for Ti) over calibration ranges of major to trace analytes.
• Detection limits well below clinical requirements; method detection limits accounted for 1:10 dilution.
• Measured concentrations in serum CRMs and urine agreed with reference values across sub-ppb to % levels.
• Continuous calibration verifications (n=9 over 8 h) showed recoveries of 95–110% (SD < 2% for most elements), confirming stability.

Benefits and Practical Applications

• Triple quadrupole ICP-MS offers superior sensitivity and interference control for challenging clinical matrices.
• Automated Reaction Finder streamlines method setup, reducing development time.
• Wide dynamic range accommodates diverse element concentrations in biofluids.
• Applicable to studies on implant degradation, trace metal exposure, and toxicological assessments.

Future Trends and Opportunities

• Integration with separation techniques (e.g., HPLC-ICP-MS) for speciation analysis of metal complexes.
• Miniaturized sample introduction to reduce volume requirements and increase throughput.
• Expanded reaction gas chemistries and software-driven interference libraries for broader analyte coverage.
• Real-time monitoring of implant wear particles and in vivo biodistribution studies.

Conclusion

The Thermo Scientific iCAP TQ ICP-MS, leveraging triple quadrupole technology and reaction-cell mass shift, delivers robust, interference-free multi-element analysis in complex biological samples. The validated method achieves low detection limits, high accuracy for titanium and other trace elements, and demonstrates long-term stability, making it a powerful tool for clinical research applications.