title: Metabolism of the recently encountered designer drug, methylone, in humans and rats.
abstract: The urinary metabolites of methylone in humans and rats were investigated by analysing urine specimens from its abuser and after administrating to rats with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards. The time-course excretion profiles of methylone and its three metabolites in rats were further investigated after a single intraperitoneal dosing of 5 mg kg-1 methylone hydrochloride. Two major metabolic pathways were revealed for both humans and rats as follows: (1) side-chain degradation by N-demethylation to the corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these metabolites, HMMC was the most abundant in humans and rats. The cumulative amount of urinary HMMC excreted within the first 48 h in rats was approximately 26% of the dose, and the amount of the parent methylone was not more than 3%. These results demonstrate that the analysis of HMMC will be indispensable for proof of the use of methylone in forensic urinalysis.
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police HQ, Osaka, Japan. htutuoppe@yahoo.co.jp
authors.forename: H T
authors.initials: HT
authors.lastname: Kamata
authors.forename: N
authors.initials: N
authors.lastname: Shima
authors.forename: K
authors.initials: K
authors.lastname: Zaitsu
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: A
authors.initials: A
authors.lastname: Miki
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: M
authors.initials: M
authors.lastname: Katagi
authors.forename: H
authors.initials: H
authors.lastname: Tsuchihashi
mesh_terms: D000328:Adult; D000818:Animals; D002849:Chromatography, Gas / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D015198:Designer Drugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D008954:Models, Biological; D015394:Molecular Structure; D011427:Propiophenones / Q000138:chemical synthesis / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D015198:Designer Drugs; D011427:Propiophenones; C047806:monomethylpropion; D008694:Methamphetamine; C400939:methylone