An evaluation of paper chromatography for measuring the levels of radiochemical impurities in 99mTc Medronate Injection

Background: The European Pharmacopoeia specifies Instant Thin‐Layer Chromatography Silica Gel (ITLC‐SG) as the stationary phase for measuring radiochemical impurities in 99mTc Medronate. The Pall Corporation has stopped manufacturing ITLC‐SG. Aim: To investigate chromatography papers as alternatives to ITLC‐SG. Experimental: The resolution of the main 99mTc Medronate and impurity peaks were compared on five Whatman papers (1CHR, 31ET, 3MM, 4CHR and 54SFC) using the pharmacopoeial mobile phases: methyl ethyl ketone for detecting 99mTc pertechnetate impurity and sodium acetate solution (136 g/l) for detecting hydrolysed reduced and colloidal 99mTc impurities. The effects of three sample spot treatments (wet, hot dried and air dried) on the distribution of the radiochemical impurities were compared. The levels of radiochemical impurities measured in samples of 99mTc Medronate were compared. Results: The highest resolutions were obtained with 1CHR, 4CHR and 54SFC. Sample spot drying resulted in the measurement of artifactually high levels of 99mTc pertechnetate impurity. When analysing 99mTc Medronate, erroneously high levels of colloidal and 99mTc pertechnetate impurities were measured with 1CHR and 4CHR. Conclusions: 54SFC paper is a suitable alternative to ITLC‐SG for measuring radiochemical impurities in 99mTc Medronate. The sample spot should be wet when the paper strip is placed in the chromatography tank. Copyright © 2009 John Wiley & Sons, Ltd. The European Pharmacopoeia specifies Instant Thin‐Layer Chromatography Silica Gel (ITLC‐SG) as the stationary phase for measuring radiochemical impurities in 99mTc Medronate. The Pall Corporation has stopped manufacturing ITLC‐SG. Five Whatman papers (1CHR, 31ET, 3MM, 4CHR and 54SFC) were evaluated as possible alternatives. The 54SFC is a suitable alternative to ITLC‐SG for measuring radiochemical impurities in 99mTc Medronate. The sample spot should be wet when the paper strip is placed in the chromatography tank. Copyright © 2009 John Wiley & Sons, Ltd.