title: Identity confirmation of 99mTc-MAG3, 99mTc-sestamibi and 99mTc-ECD using radio-LC-MS.
abstract: Due to the low concentrations in which 99mTc-radiopharmaceuticals are obtained (4-40 ng/ml), confirmation of the identity of these tracer agents in the European Pharmacopoeia is generally performed only indirectly by assessment of their retention times on RP-HPLC. We have investigated whether it is possible to obtain more direct proof of the identity of technetium-99m labelled radiopharmaceuticals using radio-LC-MS. As representative examples, negatively charged 99mTc-MAG3, positively charged 99mTc-Sestamibi and neutral 99mTc-ECD were used. The three technetium-99m radiopharmaceuticals were prepared in several conditions to obtain variable relative amounts of radiochemical impurities and variable concentrations of the complexes (pico- to nanomolar). The preparations were analyzed on a reversed phase C18 HPLC column using a radio-LC-MS system equipped with a time of flight mass spectrometer with electrospray ionization in positive (99mTc-Sestamibi, 99mTc-ECD) or negative (99mTc-MAG3, 99mTc-ECD) mode. For each of the studied complexes, the main peak in the radiometric channel coincided with the expected molecular ion mass of the corresponding technetium complex in the mass spectrometer channel. The relative error on the measured accurate mass was in the range of 10 ppm. The identity of several radiochemical impurities of the three technetium complexes was also confirmed or established. It is concluded that radio-LC-MS can be a sensitive aid in quality control of 'no carrier added' radiopharmaceuticals.
authors.affiliation: Laboratory of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Verduyckt
authors.forename: Davy
authors.initials: D
authors.lastname: Kieffer
authors.forename: Dieter
authors.initials: D
authors.lastname: Huyghe
authors.forename: Bernard
authors.initials: B
authors.lastname: Cleynhens
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D003545:Cysteine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D015609:Organotechnetium Compounds / Q000032:analysis* / Q000737:chemistry; D017263:Technetium Tc 99m Mertiatide / Q000032:analysis* / Q000737:chemistry; D017256:Technetium Tc 99m Sestamibi / Q000032:analysis* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D015609:Organotechnetium Compounds; D017263:Technetium Tc 99m Mertiatide; D017256:Technetium Tc 99m Sestamibi; C059659:technetium Tc 99m bicisate; D003545:Cysteine