Premium
An improved assay for 68 Ga‐hydroxide in 68 Ga‐DOTATATE formulations intended for neuroendocrine tumour imaging
Author(s) -
Ali Masood,
Hsieh William,
Tsopelas Chris
Publication year - 2015
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3318
Subject(s) - chemistry , sodium hydroxide , chromatography , impurity , solvent , thin layer chromatography , hydroxide , tetrabutylammonium hydroxide , hydrochloric acid , high performance liquid chromatography , size exclusion chromatography , nuclear chemistry , inorganic chemistry , enzyme , biochemistry , organic chemistry
The objective of this study was to identify a more rapid assay for 68 Ga(OH) 3 impurity in 68 Ga‐DOTATATE formulations. Three methods were used to prepare 68 Ga(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 68 Ga(OH) 3 was by titrating 68 Ga 3+ 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 68 Ga‐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 68 Ga(OH) 3 impurity located at the origin, from 68 Ga‐DOTATATE plus 68 Ga 3+ 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 % 68 Ga(OH) 3 in 68 Ga‐DOTATATE in 12 min, 13 min earlier than the pharmacopoeial method. This time efficiency resulted in a surplus of 12% 68 Ga‐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.