Urinary excretion of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats.
The urinary concentrations of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), specifically 4-hydroxy-3-methoxymethamphetamine sulfate (HMMA-Sul) and 4-hydroxy-3-methoxymethamphetamine glucuronide (HMMA-Glu), have been directly measured in both MDMA users and rats by an established liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) procedure. The concentrations of these conjugates in urine from MDMA users (n = 25) ranged from 6.5 to 202 microM (from 1.8 to 55.6 microg ml(-1)) for HMMA-Sul and from 1.3 to 87.0 microM (from 0.5 to 32.3 microg ml(-1)) for HMMA-Glu, and the ratio of HMMA-Sul to HMMA-Glu ranged from 1.6 to 9.9 (3.1 +/- 1.8). These results demonstrate that the sulfation is quantitatively more significant than the glucuronidation for HMMA in humans. In rats, in contrast, almost all the conjugated HMMA (>99%) was excreted as the glucuronide. These findings indicate that hydrolysis should be carefully made in urine analysis by gas chromatography (GC) or gas chromatography-mass spectrometry (GC-MS) by using either an acid or an enzyme possessing both sulfatase and beta-glucuronidase activities. It is concluded that a considerable interspecies variation exists in the conjugation of HMMA between humans and rats.
Shima
N
N
Forensic Science Laboratory, Osaka Prefectural Police Headquarters, Osaka, Japan. nori6499@amber.plala.or.jp
Katagi
M
M
Kamata
H
H
Zaitsu
K
K
Kamata
T
T
Nishikawa
M
M
Miki
A
A
Tsuchihashi
H
H
Sakuma
T
T
Nemoto
N
N
D015104:3,4-Methylenedioxyamphetamine / Q000737:chemistry / Q000652:urine*; D000818:Animals; D020719:Glucuronides / Q000652:urine*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000652:urine*
D020719:Glucuronides; D013431:Sulfates; C079646:4-hydroxy-3-methoxymethamphetamine; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine