title: RP-HPLC separation of the diastereomers of technetium-99m labelled tropanes and identity confirmation using radio-LC-MS.
abstract: 99mTc-TRODAT-1 (technetium(V)-oxo-2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]]amino]-ethanethiolato(3-)) and 99mTc-TRODAT-M, the 4-methylphenyl derivative of 99mTc-TRODAT-1, are at this moment being evaluated in clinical trials as imaging agents for the central nervous dopamine transporter system. Both compounds are formed as a mixture of two major diastereomers. As the tracer concentration in preparations for clinical investigations is very low (30-150 pmol/ml), identification of these 99mTc-complexes was, up to now, carried out indirectly using X-ray diffraction analysis of the corresponding rhenium complexes which can be synthesized in gram amounts. In this study, we developed a convenient and practical reversed phase HPLC-method for purification and isolation of the respective diastereomers of 99mTc-TRODAT-1 and three of its derivatives using mixtures of solvents which are compatible with biological studies, i.e. aqueous buffers and ethanol. Furthermore, direct identity confirmation of the 99mTc-complexes using radio-LC-MS was successfully elaborated.
authors.affiliation: Radiopharmacy, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. alfons.verbruggen@uz.kuleuven.ac.be
authors.forename: H P
authors.initials: HP
authors.lastname: Vanbilloen
authors.forename: B J
authors.initials: BJ
authors.lastname: Cleynhens
authors.forename: T J
authors.initials: TJ
authors.lastname: de Groot
authors.forename: A
authors.initials: A
authors.lastname: Maes
authors.forename: G M
authors.initials: GM
authors.lastname: Bormans
authors.forename: A M
authors.initials: AM
authors.lastname: Verbruggen
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D013237:Stereoisomerism; D013667:Technetium / Q000032:analysis* / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014326:Tropanes / Q000032:analysis* / Q000737:chemistry*
chemical_list: D014326:Tropanes; D013667:Technetium