In vivo formation of aromatic hydroxylated metabolites of 3,4-(methylenedioxy)methamphetamine in the rat: identification by ion trap tandem mass spectrometric (MS/MS and MS/MS/MS) techniques.
Aromatic hydroxylation has been established as a pathway for the in vivo metabolism of 3,4-(methylenedioxy)methamphetamine (MDMA) in the rat. Hydroxylation occurred at positions 2, 5 and 6 of the 3,4-methylenedioxyphenyl ring, but is favored at the 6 position. All three regioisomers of both hydroxy-MDMA and hydroxy-3,4-(methylenedioxy)amphetamine (hydroxy-MDA) were detected in the rat liver when 20 mg kg-1 of MDMA was administered. However, 6-hydroxy-MDMA and 6-hydroxy-MDA were the only hydroxylated metabolites detected in the rat brain and plasma and no hydroxylated metabolites were detected in the urine. The hydroxylated metabolites were identified by co-injection of synthetic reference compounds and comparison of the mass spectra of the trifluoroacetyl derivatives of the metabolites with the synthesized reference compounds. The regioisomers of both hydroxy-MDMA and hydroxy-MDA could not be distinguished by either single-stage or two-stage mass analysis. However, employment of a third stage of mass analysis produced distinctly different mass spectra for each of the three regioisomers.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84108.
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D015104:3,4-Methylenedioxyamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001923:Brain Chemistry; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D011919:Rats, Inbred Strains
C073631:6-hydroxy-N-methyl-3,4-methylenedioxyamphetamine; D015104:3,4-Methylenedioxyamphetamine; C062690:N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane; D018817:N-Methyl-3,4-methylenedioxyamphetamine