Enantioselective quantitation of the ecstasy compound (R)- and (S)-N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma and urine
| Autor: | Claudia Marx, Matthias Schwab, Gerd Mikus, Georg Grön, Karl Artur Kovar, Jochen Buechler, Manfred Spitzer, Leo Hermle, Beate Fischer |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Glucuronate Clinical Biochemistry Pilot Projects Urine Biochemistry High-performance liquid chromatography Analytical Chemistry Double-Blind Method Humans Solid phase extraction 3 4-Methylenedioxyamphetamine Chromatography High Pressure Liquid Cross-Over Studies Chromatography Chemistry Area under the curve Reproducibility of Results Stereoisomerism Cell Biology General Medicine Middle Aged Spectrometry Fluorescence Stereoselectivity Enantiomer Quantitative analysis (chemistry) |
| Zdroj: | Journal of Chromatography B. 793:207-222 |
| ISSN: | 1570-0232 |
| DOI: | 10.1016/s1570-0232(03)00266-6 |
| Popis: | An enantioselective HPLC method has been developed and validated for the stereospecific analysis of N -ethyl-3,4-methylenedioxyamphetamine (MDE) and its major metabolites N -ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA). These compounds have been analyzed both from human plasma and urine after administration of 70 mg pure MDE-hydrochloride enantiomers to four subjects. The samples were prepared by hydrolysis of the o -glucuronate and sulfate conjugates using β-glucuronidase/arylsulfatase and solid-phase extraction with a cation-exchange phase. A chiral stationary protein phase (chiral-CBH) was used for the stereoselective determination of MDE, HME and MDA in a single HPLC run using sodium dihydrogenphosphate, ethylendiaminetetraacetic acid disodium salt and isopropanol as the mobile phase (pH 6.44) and fluorimetric detection ( λ ex 286 nm, λ em 322 nm). Moreover, a suitable internal standard ( N -ethyl-3,4-methylenedioxybenzylamine) was synthesized and qualified for quantitation purposes. The method showed high recovery rates (>95%) and limits of quantitation for MDE and MDA of 5 ng/ml and for HME of 10 ng/ml. The RSDs for all working ranges of MDE, MDA and HME in plasma and urine, respectively, were less than 1.5%. After validation of the analytical methods in plasma and urine samples pharmacokinetic parameters were calculated. The plasma concentrations of ( R )-MDE exceeded those of the S -enantiomer (ratio R : S of the area under the curve, 3.1) and the plasma half time of ( R )-MDE was longer than that of ( S )-MDE (7.9 vs. 4.0 h). In contrast, the stereochemical disposition of the MDE metabolites HME and MDA was reversed. Concentrations of the ( S )-metabolites in plasma of volunteers were much higher than those of the ( R )-enantiomers. |
| Databáze: | OpenAIRE |
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