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

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.