Characterization of Rare Earth Elements used for Radiolabeling Applications by ICP-QQQ

Importance of the Topic

Radiolabeled rare earth elements are critical in modern pharmaceutical agents and imaging applications, offering targeted delivery and precise tracing of radioactive signals. High demand for pure radio-lanthanide compounds necessitates robust analytical methods to ensure starting materials meet strict purity requirements and to guide development of separation processes.

Objectives and Study Overview

This study aims to apply triple quadrupole ICP-MS (ICP-QQQ) to characterize trace impurities of rare earth elements (REEs) in bulk REE matrices relevant to radiolabeling. Key goals include measuring detection limits for trace REEs in high concentration matrices, optimizing mass-shift interference removal, and demonstrating quality assurance of irradiated targets.

Methodology

Samples were prepared with trace REE standards (1 ppt to 100 ppb) in 10 ppm solutions of neighboring REE matrices. Extraction chromatography using lanthanide‐selective resin was performed to separate target lanthanides from bulk material. The ICP-QQQ was operated in MS/MS mode with oxygen cell gas to remove hydride, oxide, and peak-tailing interferences, employing on-mass and mass-shift measurement strategies.

Used Instrumentation

• Agilent 8800 Triple Quadrupole ICP-MS
• Glass concentric nebulizer and quartz spray chamber
• Quartz torch with 2.5 mm i.d. injector
• Nickel-tipped interface cones
• MS/MS mode with O2 reaction gas at 0.3 mL/min and RF power 1550 W

Main Findings and Discussion

ICP-QQQ achieved detection limits in the low parts-per-trillion range for most REEs: for example, 2.1 ppt for Tb in a 10 ppm Gd matrix and sub-20 ppt for Ce, Pr, Tm, and Lu in their respective matrices. Higher DLs were observed for Ho in Dy (1.1 ppb) due to limited reactive gas formation of HoO+ and peak tailing. The method outperformed conventional single quadrupole ICP-MS by reducing background from polyatomic and tailing interferences by over seven orders of magnitude.

Chemical separation experiments using LN resin demonstrated effective isolation of Tb from a 4.5×10^4 excess of Gd, with minimal cross-contribution at m/z 159. Post-irradiation analysis of a Gd2O3 target used for 155Tb production identified La and Ce impurities at ppm levels in the initial sample, which were reduced below background after purification.

Benefits and Practical Applications

• Enables reliable QA profiling of trace REE impurities in high-purity lanthanide materials
• Supports development of radiochemical separation schemes under realistic non-radioactive conditions
• Allows post-separation assessment of stable impurities in irradiated targets to predict labeling efficiency and side-product formation

Future Trends and Opportunities

Further improvements may be realized by exploring alternative reaction gases such as N2O or NH3 to enhance oxide formation and interference removal. Integration of ICP-QQQ into routine radiopharmaceutical production workflows can streamline QA/QC and facilitate recycling of enriched lanthanide targets. Advances in high-resolution mass spectrometry will continue to drive down detection limits for ultra-trace impurity analysis.

Conclusion

The application of ICP-QQQ in MS/MS mode with O2 cell gas provides an effective solution for precise measurement of ppq- to ppt-level REE impurities in bulk matrices. This method offers substantial interference removal compared to single quadrupole ICP-MS, enabling robust quality assurance of materials used in radiolabeling and guiding the optimization of separation processes for high-purity radio-lanthanide production.

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