HPLC Radiochemical Detector Linearity: An Important yet often ignored measurement

Objectives An important element in the validation of an analytical method is an understanding of the linear range of the method. Historically, this has not been the case for radiochemical detectors used in HPLC testing of PET drugs. In addition, it is not known if the linearity of the radiochemical detector response is unique to each product, or if the linearity results from one product may be used in others.

Methods The HPLC system was equipped with a UV detector and a shielded sodium iodide crystal. Targeted amount of radioactivity were injected onto the HPLC system, for example, 1000 µCi to 2.5 µCi. Products selected for this study included: (a) FDG, (b) NaF, (c) FLT. Well-characterized, non-radioactive, reference standards were co-injected with the PET drug solution to ensure proper identification of the radioactive peaks of interest.

Results For each product tested, the linearity of the radiochemical detector response was confirmed within a product concentration range of 0.5-50 mCi/mL. Parameters that may affect the linearity of the radiochemical detector are flow rate and peak symmetry. This study demonstrates that a variable flow rate (1.0 and 0.75 mL/min) and different peak symmetry did not cause the linearity of the detector to change.

Conclusions Operations for TLC, GC, and UV measurements within the PET Radiochemistry laboratory always include some form of linearity measurements. However, little thought is traditionally given to the “second” component of the HPLC system: the radiochemical detector. With almost all PET biomarkers the determination of radiochemical purity (RCP) is via HPLC yet performance qualification is typically minimal. The results from this study demonstrate that the radiochemical detector response is linear over the useful range of the instrument and over a wide range of specific concentrations. In addition, the results indicate that the linear response is the same for different PET drug products possessing the same radionuclide. This should eliminate the need to perform separate linearity determinations for each PET drug.