title: High performance liquid chromatography-tandem mass spectrometry method for ex vivo metabolic studies of a rhenium-labeled radiopharmaceutical for liver cancer.
abstract: The radio-isotope rhenium-labeled N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl] octadecanoate) ligand (188Re-MN-16ET) is a novel therapeutic agent under preclinical evaluation for hepatoma. A reversed-phase high performance liquid chromatography coupled with a tandem mass spectrometric analysis method and diode array detector (DAD) involving a T type splitter was developed to characterize this pharmaceutical in rat liver tissue solution and determine its biotransformation rate. The separation was accomplished on a C18 column (chromolith silica, 4.6 mm x 100 mm) using an acetonitrile-ammonium acetate buffer gradient as the mobile phase. The detection was achieved by DAD set at 250nm and tandem mass spectrometry using electrospray ionization in the positive ion mode. Re-MN-16ET displayed a retention time of 23.2 min and a transition ion pair corresponding to m/z677 --> 631 for multiple reaction monitoring. Its biotransformation reaction in rat liver homogenate proceeded for 90 min in a 37°C water bath. The characterization was conducted using aliquots that were extracted and concentrated from the reaction mixture for various incubation times. Re-MN-16ET exhibited a biotransformation half-life (t1/2) of 8-9 min in liver tissue solution and was almost completely exhausted after 90 min. Two of its metabolites, consisting of the Re-labeled carboxylic acid derivative, predominately, and its corresponding demetallized disulfide ligand were found in the liver homogenate, providing a metabolism pathway for the radio-pharmaceutical.
authors.forename: Wei-Hsi
authors.initials: WH
authors.lastname: Chen
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Liao
authors.forename: Tsai-Yueh
authors.initials: TY
authors.lastname: Luo
authors.forename: Yu
authors.initials: Y
authors.lastname: Chang
authors.forename: Lee-Chung
authors.initials: LC
authors.lastname: Men
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056831:Coordination Complexes / Q000032:analysis* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000032:analysis / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D012211:Rhenium / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*
chemical_list: C569624:188Re-MN-16ET; D056831:Coordination Complexes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium