Abstract

The sensitive technique of gas chromatography-mass spectrometry was used to detect and identify metabolites of methamphetamine and fenfluramine in rat tissue after i.p. administration of doses which cause tissue monoamine depletion. Methamphetamine (90µmol/kg) causes a long-lasting depletion of heart norepinephrine and a shorter-lasting depletion of brain norepinephrine and 5-hydroxytryptamine, whereas fenfluramine (90µmol/kg) produces a selective and long-lasting depletion of brain 5-hydroxytryptamine. After production of trimethylsilyl heptafluorobutyryl derivatives of these drugs and their metabolites, the technique of mass fragmentography facilitated the detection and identification of the N-dealkylated metabolites of methamphetamine, amphetamine and p-hydroxyamphetamine in tissues. The N-dealkylated metabolite of fenfiuramine, norfenfluramine, was similarly detected in tissue homogenates of rats killed up to 24 hours after injection. The N-dealkylation of both drugs involves a stereoisomeric dependence and gives rise to metabolites which persist in tissues and conceivably are involved in tissue monoamine depletion.