Speciation analysis of Tc radiopharmaceuticals by HPLC-ICP-MS and HPLC-ESI-HRMS

Abstract

Its easy accessibility, ideal physical properties and the multifaceted redox chemistry made ^99mTc the most important radionuclide for SPECT (single-photon emission computed tomography) in nuclear medicine. Unfortunately, small concentrations used in scintigraphy are also limiting analytical techniques to perform routine quality controls and to support the development of novel tracers. In this work, speciation analysis via liquid chromatography (LC) coupled with elemental and molecular mass spectrometry is developed for novel and established Tc radiopharmaceuticals to enable direct identification, characterization, and quantification. Here, an Orbitrap-based ESI-MS method was used to attain high mass resolutions and high mass accuracies for compound identification. RP-HPLC-ICP-MS was employed for the separation and sensitive detection of Tc species. Due to a lack of Tc standards, the previously introduced “isobaric dilution analysis” was modified and applied in an on-line post-column dilution approach. Besides the expected tracers, various Tc impurities were detected and calibrated in a non-target approach. The presented methods allow fast on-site quality controls of commercially available tracers, but further promote the characterization of novel experimental tracers in nuclear medicine without the need of “cold” reference compounds.