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

J Chromatogr B Biomed Sci Appl. 1999 Dec 24;736(1-2):61-6. doi: 10.1016/s0378-4347(99)00439-9.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / analysis*
  • Antineoplastic Agents / blood
  • Brain Chemistry
  • Carbon Radioisotopes
  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Isoquinolines / analysis*
  • Isoquinolines / blood
  • Isoquinolines / pharmacokinetics
  • Mice
  • Myocardium / chemistry
  • Receptors, GABA-A / analysis
  • Receptors, GABA-A / metabolism
  • Species Specificity

Substances

  • Antineoplastic Agents
  • Carbon Radioisotopes
  • Isoquinolines
  • Receptors, GABA-A
  • PK 11195