Alternative methods for radiochemical purity testing in radiopharmaceuticals

The radiochemical purity (RCP) testing is as prerequisite for radiopharmaceuticals before the administration to the patient. Because time is critical in nuclear medicine, emphasis should be given to the radiochemical quality control procedures, in order to obtain the maximum amount of information in the minimum period of time. Radiochemical purity is defined as the proportion of the total radioactivity in the product that is present in the specified chemical form. Usually, the RCP is evaluated by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The most widely used technique for RCP determination in radiopharmaceutical preparations is TLC-aluminium (TLC-Al), instant thin layer chromatography-silica gel (ITLC-SG) and paper chromatography (PC). Indeed, many of the pharmacopeial methods use these techniques. The purpose of the present study was to evaluate different chromatographic systems for RCP in 67Ga-Citrate, 111In-Octreotide, 177Lu-DOTATATE and 153Sm-HA. PC was performed with 3MM/1MM Whatman plates, TCL-Al sheets from Merck and ITLC-SG sheets from Pall Corporation and Varian Inc. The mobile phases were 0.16 mol.L-1 sodium acetate, 0.9% sodium chloride (p/v), 0.1 mol.L-1 sodium citrate buffer, 0.2 mol.L-1 EDTA, methanol:0.4 mol.L-1 ammonium acetate (1:1) mixture, and pyridine:ethanol:water (1:2:4) mixture. The samples were placed on plates in triplicate and immediately put into pre-saturated chambers with the mobile phase. After the chromatographic separation, the plates were dried and cut into 7, 10 or 12 segments and each one was separately measured in a gamma counter during 0.20 minutes (set on the radioisotope window). The results in the gamma counter were expressed in counts per minute (cpm). The chromatographic systems for 177Lu-DOTATATE and 153Sm-HA gave the best performances in 0.1 mol L-1 sodium citrate buffer/TLC-Al and 0.9% (p/v) sodium chloride/Whatman 1, respectively. 111In-Octreotide showed better results in 0.2 mol L-1 EDTA/TLC-Al. Two systems were evaluated for 67Ga-Citrate, 3MM Whatman PC with 0.16 mol.L-1 sodium acetate and pyridine:ethanol:water (1:2:4) mixture. The best performance was obtained with 0.16 mol.L-1 sodium acetate. The established limits of RCP vary from 95% to 97% and all the results showed to be in accordance with the specifications for each analyzed product. (author)