Identification of the Dopaminergic Neurotoxin 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline in Human Blood after Intake of the Hypnotic Chloral Hydrate

Abstract

1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo), a potent toxin toward dopaminergic neurons, readily originatesin vitrofrom the biogenic amine tryptamine and the unnatural aldehyde chloral. For this reason, this heterocycle has been postulated to be formed endogenously in humans after administration of the hypnotic chloral hydrate or after exposure to the industrial solvent trichloroethylene by a spontaneous chemical ring closure reaction. In this paper, we report on the first identification of TaClo in blood samples of patients treated orally with chloral hydrate. Using a specific and sensitive gas chromatographic screening procedure based upon electron-capture and mass-selective detection, TaClo was determined after conversion to its volatile trifluoroacetyl derivative. The identity of TaClo in humans was clearly demonstrated by GC–MS analysis in selected-ion-monitoring mode, by the characteristic chlorine isotopic pattern of the molecular ion.