Stereospecific analysis of ecstasy-like N-ethyl-3,4-methylenedioxyamphetaine andits metabolites in humans

摘要

A chiral HPLC method has been developed for the ecstasy analogue (R,S ~-N-ethYl-3.4-methylenedioxyamphetamine (MDE) and its metabolites o-glucuronyl~(R,s)~N~ethyl4hydroxy3methOxy etamine (HME) and (R,S)-3,4-methylene-dioxyamphetamine (MDA) in human plasma. The chiral discrimination of the compounds was carried out with an enantioselective HPLC method using f3-cyclodextrin in the mobile phase for MDE and MDA and a chiral protein phase (chiral-CBH) for LIME. MDE and MDA were detected fiuQrlm~Lncally at 322 nm. while the major metabolite HME was selectively determined by electrochemical detection at +600 mV. After hydrolysis of the conjugates using f3-glucuronidase/ arylsulfatase and solid-phase extraction with a cation-exchange phase for sample preparation high recovery rates of more than 95% were yielded. The limit of quantitation for the enantiomers of MDE and its metabolites in plasma were between 1.2 (MDA) and 16 ng/mi (HME) and the relative method standard deviations (~ ,Table I) were less than 3%. The methods described have been used successfully in the enantioselective quantitation of the compounds in plasma samples obtained from six healthy volunteers in a clinical srudy after oral administration of 140 mg racemic MDE hydrochloride. Significant differences were found in the plasma concentrations of the examined stereoisomers. Whereas the R-enanriomer of the parent substance, MDE, was predominant in the plasma samples investigated, higher plasma concentrations of the S-enantiomers of the metabolites MDA and LIME were measured.