Chiral separation of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling and its effects on oxidative stress status in rat liver.
Tiago C Lourenço, Graziela C Bósio, Neila M Cassiano, Quezia B Cass, Regina L M Moreau
Journal of Pharmaceutical and Biomedical Analysis January 25, 2013 DOI: 10.1016/j.jpba.2012.01.025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | Racemic MDMA (R)-(-)-MDMA (S)-(+)-MDMA |
| Topics | MDMA |
| Key findings | The (R)-(-)-MDMA enantiomer, not the (S)-(+)-MDMA enantiomer, appears responsible for the liver glutathione depletion and increased malondialdehyde production seen with racemic MDMA in rats, indicating enantiomer-specific oxidative stress in the liver. |
Abstract
This work reports the multimiligram separation of 3,4-methylenedioxy-methamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling. The effect of both enantiomers compared to the racemic mixture was examined on the oxidative stress status of rat liver. The enantiomeric purification was performed using a based cyclodextrin chiral selector and methanol:ammonium acetate buffer (pH 6.0, 100mM) (30:70, v/v) as mobile phase. The average mass rate obtained was 40.0mg/day, providing 45.0mg of the (R)-(-)-MDMA (e.r. 99.0%) and 75.0mg (e.r. 96.0%) of (S)-(+)-MDMA. Racemic MDMA and both enantiomers were administered per orally to Wistar rats and oxidative stress status parameters, as liver total glutathione levels and malondialdehyde (MDA) production in liver were evaluated. There was a significant decrease in hepatic glutathione content in the racemic MDMA and the (R)-(-)-MDMA-treated rats when compared to the control and to (S)-(+)-MDMA. These results demonstrate that the R-enantiomer is the enantiomer that contributes to the depletion of hepatic glutathione induced by the racemic mixture. The high reactivity of the R-enantiomer of MDMA in the liver can also be observed in animals treated with (R)-(-)-MDMA. The production of malondialdehyde (MDA) by (R)-(-)-MDMA was significantly higher when compared to the other treated groups and control.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Synthesis of R- and S-MDMA via nucleophilic ring-opening of homochiral N-tosylaziridines Australian Journal of Chemistry July 11, 2023
- Swim in the Chiral Pool: MDMA and MDA Enantiomers from Alanine-Derived Precursors. ACS Omega June 6, 2023
- Molecular basis of the selective binding of MDMA enantiomers to the alpha4beta2 nicotinic receptor subtype: synthesis, pharmacological evaluation and mechanistic studies. European journal of medicinal chemistry June 23, 2014
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