title: Purification of the precursor for the automated radiosynthesis of [18F]FCWAY by counter-current chromatography.
abstract: Radiolabeled FCWAY (N-(2-[4-(2-methoxyphenyl)piperazino])-N-(2-pyridinyl) trans-4-fluorocyclohexanecarboxamide) was prepared for human positron emission tomography (PET) studies by a simple one-step radiosynthesis. The LC-MS analysis of the products indicated that it contained impurities which may interfere with FCWAY uptake of 5-HT1A receptors and that these impurities were derived from an impurity originally present in the precursor preparation. Since preparative HPLC failed to resolve one of the impurities from the precursor, preparative-scale high-speed counter-current chromatography (HSCCC) was used for purification of this FCWAY precursor. A suitable two-phase solvent system composed of cyclohexane-ethyl acetate-methanol-water at a volume ratio of 1:1:1:1 or 4:5:4:5 was selected based on the partition coefficients of the precursor and impurity as determined by a LC-MS method. Using the second solvent ratio of 4:5:4:5 with the organic phase as a mobile phase, a 2.57 g amount of precursor preparation was successfully purified yielding 2.2 g of the pure precursor by a single run.
authors.affiliation: PET Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bldg 10, Rm 1C401, 10 Center Drive MSC 1180, Bethesda, MD 20892, USA. yma@mail.cc.nih.gov
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Bik-Kee
authors.initials: BK
authors.lastname: Vuong
authors.forename: Michael
authors.initials: M
authors.lastname: Channing
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Ito
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D003377:Countercurrent Distribution / Q000379:methods*; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000302:isolation & purification; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000302:isolation & purification; D010879:Piperazines / Q000138:chemical synthesis* / Q000302:isolation & purification
chemical_list: D003510:Cyclohexanes; D005462:Fluorine Radioisotopes; C493883:N-(2-(4-(2-methoxyphenyl)piperazino))-N-(2-pyridinyl) trans-4-fluorocyclohexanecarboxamide; D010879:Piperazines