Determination of β-Carboline Derivatives in Biological Samples by High-Performance Liquid Chromatography with Fluorescence Detection

An assay procedure for measuring plasma, urine, and feces levels of seven β-carbolines and possible metabolites is described. The drugs are extracted with diethylether or, alternatively, with a commercially available automated extraction device after adding an appropriate internal standard. Separation from matrix constituents is performed by reversed-phase high-performance liquid chromatography (HPLC) followed by fluorescence detection. The carboxylic acid metabolites of the β-carbolines have to be esterified before HPLC measurement. The detection limits are 0.2 ng/mL for β-carbolines and 2 ng/mL for their metabolites. Plasma levels and pharmacokinetic parameters of six different β-carbolines in healthy male volunteers following iv or po treatment are described. Total clearance ranged from 17 to 52 mL/min/kg and the terminal half-life ranged from 1 to 4 h. The absolute bioavailability exhibited a range from <1 to 61%.