Radiochemical Purity and Identity in Radiopharmaceuticals: Design and Improvement of Quality Control Methods by HPLC

Abstract

The radiopharmaceutical supply chain involves rigorous quality control tests to assure products are safe and effective to use in the clinic. However, one of the key challenges for analytical methods in radiopharmacy is the narrow time frame where the analysis must be completed due to the limited half-life of radiomolecules. Radiochemical purity and identity are critical tests to control the success of radiolabeling. These parameters are easily determined by thin-layer chromatography methods (TLC) in some widely used molecules such as [18F]FDG. However, for new diagnostic and therapeutic agents with more complex radiolabeling steps, it is critical to have better separations to identify impurity peaks only detectable using higher sensitive methods. This chapter will present the keys to designing and improving high-performance liquid chromatography (HPLC) methods for radiopharmaceutical analysis, with practical examples of method optimization. It will also be reviewed how to determine the main parameters necessary for the validation of an analytical method, and finally, some approaches to the use of liquid chromatography coupled with mass detectors in tandem (LC-MS/MS) during the development of radiopharmaceuticals will be presented.