Stereospecific analysis of ecstasy-like N-ethyl-3,4-methylenedioxyamphetamine and its metabolites in humans.
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-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and (R,S)-3,4-methylenedioxyamphetamine (MDA) in human plasma. The chiral discrimination of the compounds was carried out with an enantioselective HPLC method using beta-cyclodextrin in the mobile phase for MDE and MDA and a chiral protein phase (chiral-CBH) for HME. MDE and MDA were detected fluorimetrically at 322 nm, while the major metabolite HME was selectively determined by electrochemical detection at +600 mV. After hydrolysis of the conjugates using beta-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/ml (HME) and the relative method standard deviations (V(xO), Table 1) 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 study after oral administration of 140 mg racemic MDE hydrochloride. Significant differences were found in the plasma concentrations of the examined stereoisomers. Whereas the R-enantiomer of the parent substance, MDE, was predominant in the plasma samples investigated, higher plasma concentrations of the S-enantiomers of the metabolites MDA and HME were measured.
Department of Pharmaceutical Chemistry, Tübingen, Germany.
M
M
Brunnenberg
K A
KA
Kovar
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000737:chemistry; D012680:Sensitivity and Specificity
D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine