High-performance liquid chromatographic determination of [C-11]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-chlorophe nyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ([C-11]PK 11195 ) is described. The method was successfully applied for plasma and tissue a nalysis after i.v. injection of [C-11]PK 11195 in mice and for plasma analy sis after administration of [C-11]PK 11195 to humans. Separation is effecte d on a RP-C-18 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 2x2 in. NaI(Tl) det ector. For humans rapid metabolisation of [C-11]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 ext ensive metabolisation rate in mice (up to 42% at 10 min post injection of [ C-11]PK 11195), no C-11-labelled metabolites could be detected in the extra cts of brain and heart. (C) 1999 Elsevier Science B.V. All rights reserved.