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

Abstract

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 µM (from 1.8 to 55.6 µg ml⁻¹) for HMMA-Sul and from 1.3 to 87.0 µM (from 0.5 to 32.3 µg 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 β-glucuronidase activities. It is concluded that a considerable interspecies variation exists in the conjugation of HMMA between humans and rats.

Keywords :

• 3,4-Methylenedioxymethamphetamine (MDMA)
• 4-hydroxy-3-methoxymethamphetamine (HMMA)
• Sulfation
• Glucuronidation
• Species variation