Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites.

1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. 4. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. 5. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.