title: High-performance liquid chromatographic determination of [11C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide in mouse plasma and tissue and in human plasma.
abstract: The high-performance liquid chromatographic determination of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ([11C]PK 11195) is described. The method was successfully applied for plasma and tissue analysis after i.v. injection of [11C]PK 11195 in mice and for plasma analysis after administration of [11C]PK 11195 to humans. Separation is effected on a RP-C18 column, using a mixture of acetonitrile-water-triethylamine (65:35:0.5, v/v). Quantitative measurements of radioactivity are performed on a one-channel gamma-ray spectrometer equipped with a 2 x 2 in. NaI(Tl) detector. For humans rapid metabolisation of [11C]PK 11195 was observed. At 5, 20 and 35 min post injection 5%, 22% and 32%, respectively, of the plasma activity consisted of at least two more polar metabolites. Despite the extensive metabolisation rate in mice (up to 42% at 10 min post injection of [11C]PK 11195), no 11C-labelled metabolites could be detected in the extracts of brain and heart.
authors.affiliation: Department of Radiopharmacy, University of Gent, Belgium. filipx.devos@rug.ac.be
authors.forename: F
authors.initials: F
authors.lastname: De Vos
authors.forename: F
authors.initials: F
authors.lastname: Dumont
authors.forename: P
authors.initials: P
authors.lastname: Santens
authors.forename: G
authors.initials: G
authors.lastname: Slegers
authors.forename: R
authors.initials: R
authors.lastname: Dierckx
authors.forename: J
authors.initials: J
authors.lastname: De Reuck
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007546:Isoquinolines / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D051379:Mice; D009206:Myocardium / Q000737:chemistry; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism; D013045:Species Specificity
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195