IDENTIFICATION AND QUANTIFICATION OF THE INDOLE ALKALOID IBOGAINE IN BIOLOGICAL SAMPLES BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

A sensitive and highly selective analytical chemical method for measuring the indole alkaloid ibogaine in biological samples has been developed. The method utilizes organic extraction, derivatization with trifluoroacetic anhydride, and detection by combined gas chromatography-mass spectrometry. The deuterated analog of ibogaine, O-[Cd-3]-ibogaine, was synthesized and used as an internal standard for the method. Standard curves, constructed from variable amounts of ibogaine (50-400 ng) and a fixed amount of internal standard (250 ng) were linear. The method has an approximate detection limit of at least 20 ng/mL of tissue extract (180 ng/g tissue), with a coefficient of variation of 8 to 12.5%. Chemical stability studies with the method found that aqueous ibogaine solutions (1-10 mg/mL) could be stored at 10 degrees for up to 7 months with no more than 10% loss. The method was also used to measure brain ibogaine levels in rats 1 and 19 hr after a single dose of drug (40 mg/kg, i.p.); the results suggest a rapid disappearance of the drug after i.p. dosing. The method will help reveal the pharmacokinetic properties of this putative anti-addictive agent in animals and humans.