Development and Validation of a High-Pressure Liquid Chromatography Method for the Determination of Chemical Purity and Radiochemical Purity of a [(68)Ga]-Labeled Glu-Urea-Lys(Ahx)-HBED-CC (Positron Emission Tomography) Tracer

[Image: see text] Background: Prostate-specific membrane antigen (PSMA) has gained high attention as a useful biomarker in the imaging evaluation of prostate cancer with positron emission tomography (PET) during recent years. [(68)Ga]-labeled Glu-urea-Lys(Ahx)-HBED-CC ([(68)Ga]-PSMA-HBED-CC) is a novel PSMA inhibitor radiotracer which has demonstrated its suitability in detecting prostate cancer. Preparation conditions may influence the quality and in vivo behavior of this tracer, and no standard procedure for the quality control (QC) is available. The aim of this study was to develop a new rapid and simple high-pressure liquid chromatography method of analysis for the routine QCs of [(68)Ga]-PSMA-HBED-CC to guarantee the high quality of the radiopharmaceutical product before release. Methods: A stepwise approach was used based on the quality by design concept of the International Conference of Harmonisation Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of European Association of Nuclear Medicine, Society of Nuclear Medicine, International Atomic Energy Agency, World Health Organization, and Italian Association of Nuclear Medicine and Molecular Imaging. The developed analytical test method was validated because a specific monograph in the pharmacopoeia is not available for [(68)Ga]-PSMA-HBED-CC. Results: The purity and quality of the radiopharmaceutical obtained according to the proposed method resulted high enough to safely administrate it to patients. An excellent linearity was found between 0.8 and 5 μg/mL, with a detection limit of 0.2 μg/mL. Assay imprecision (% CV) was <2%. Conclusions: The developed method to assess the radiochemical and chemical purity of [(68)Ga]-PSMA-HBED-CC is rapid, accurate, and reproducible, allowing routinely the use of this PET tracer as a diagnostic tool for imaging prostate cancer and also assuring patient safety.