An improved assay for 68Ga‐hydroxide in 68Ga‐DOTATATE formulations intended for neuroendocrine tumour imaging

The objective of this study was to identify a more rapid assay for ⁶⁸Ga(OH)₃ impurity in ⁶⁸Ga‐DOTATATE formulations. Three methods were used to prepare ⁶⁸Ga(OH)₃ reference material (pharmacopoeial, bench titration and automated radiosynthesis), and four quality control methods for its assessment (thin layer chromatography, membrane filtration, HPLC and solid phase extraction). The optimal method of preparing ⁶⁸Ga(OH)₃ was by titrating ⁶⁸Ga³⁺ with buffered sodium hydroxide solutions to pH 5.6 ± 0.2. The precipitate was quantitatively isolated by membrane filtration (0.02 µm)/hydrochloric acid (HCl; pH 5.6) solvent, and also it remained 100% at the origin on instant thin layer chromatography with silica gel paper/HCl (pH 5.6) solvent. For ⁶⁸Ga‐DOTATATE samples, the thin layer chromatography technique was used with a single paper strip developed separately on two occasions, once in HCl (pH 5.6) and next in methanol solvent. This so‐called double‐developed (DD) method separated ⁶⁸Ga(OH)₃ impurity located at the origin, from ⁶⁸Ga‐DOTATATE plus ⁶⁸Ga³⁺ at ~R_f 0.4, and it was superior to the other methods. It assayed for the impurity similarly to the pharmacopoeial method. The advantages of the DD method were that it required inexpensive test materials and it reproducibly determined % ⁶⁸Ga(OH)₃ in ⁶⁸Ga‐DOTATATE in 12 min, 13 min earlier than the pharmacopoeial method. This time efficiency resulted in a surplus of 12% ⁶⁸Ga‐DOTATATE counts in the product vial, and this provided a contingency of radioactivity or time for the injection/imaging processes in the Nuclear Medicine Department.