Determination of xanthenone-4-acetic acid in mouse plasma by high-performance liquid chromatography

Xanthenone-4-acetic acid (XAA) was synthesised during a search for improved analogues of flavone-8-acetic acid, an antitumour agent with a unique mechanism of action but with a number of pharmacological disadvantages. We describe a simple, selective high-performance liquid chromatographic assay suitable for the detection of XAA in mouse plasma. After addition of an internal standard (3-methyl-XAA), plasma was acidified with trichloroacetic acid and extracted with toluene. After evaporation of solvent, samples were chromatographed on a C18 4-microns Novapak cartridge (mobile phase: water-acetonitrile-acetic acid, 65:35:2, v/v) using fluorescence detection. At the maximum tolerated dose of XAA (725 mumol/kg), nonlinear pharmacokinetics were observed.