3,4-dihydroxymethamphetamine (HHMA). A major in vivo 3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans

There is evidence that some heavy users of 3,4-methylenedioxymethamphetamin e (MDMA, ecstasy) show signs of neurotoxicity (a cognitive dysfunction, a l arger incidence of psychopathology). It has been postulated that the catech ol intermediates of methylenedioxyamphetamines such as 3,4-dihydroxymethamp hetamine (HHMA), a metabolite of MDMA, may play a role in their neurotoxici ty by formation of thioether adducts. This study describes the first valida ted method for HHMA determination in plasma and urine by strong cation-exch ange solid-phase extraction high-performance liquid chromatography/electroc hemical detection (HPLC/ED) analysis. The method has been applied for the d etermination of HHMA in plasma and urine samples from a clinical study in h ealthy volunteers of MDMA and provides preliminary kinetic data on this met abolite. HHMA appeared to be a major MDMA metabolite with plasma concentrat ions as high as the parent compound. Thus, HHMA C-max (154.5 mug/L) and AUC (0-24h)(1990.9 mug/L h) were similar to those obtained in previously publis hed reports for MDMA (181.6 mug/L and 1465.9 mug/L h, respectively). The 24 -h urinary recovery of HHMA accounted for 17.7% of the MDMA dose administer ed and increases the total 24 h recovery of MDMA and metabolites to 58% of the 100 mg dose administered. The determination of HHMA in plasma and urine samples is of interest in order to establish its relevance in MDMA metabol ism and its possible contribution to MDMA neurotoxicity in humans. Its vali dation showed appropriate accuracy and precision for its use in pharmacokin etic studies.