Derivatization-free determination of chiral plasma pharmacokinetics of MDMA and its enantiomers.
Dino Luethi, Deborah Rudin, Isabelle Straumann, Jan Thomann, Isidora Avedisian, Matthias E. Liechti, Urs Duthaler
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences May 1, 2024 DOI: 10.1016/j.jchromb.2024.124123 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Method development and validation Peer reviewed |
|---|---|
| Population | Human plasma from clinical study participants treated with racemic MDMA or one of its enantiomers |
| Interventions | racemic MDMA S-MDMA |
| Topics | MDMA |
| Keywords | Bioanalysis Enantioselective Pharmacokinetics Enantiomers MDMA Analysis Drug metabolism |
| Citations | 6 |
| Key points | The enantioselective method is useful for simultaneous quantification of both MDMA enantiomers in racemic treatment, but enantioselective separation is unnecessary for subjects treated with only one enantiomer because no chiral inversion occurs. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography-tandem mass spectrometry method for the quantification of MDMA and its psychoactive phase I metabolite 3,4-methylenedioxyamphetamine (MDA) in human plasma were developed and validated. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range was 0.5-500 ng/mL for the achiral analysis of both analytes, 0.5-1,000 ng/mL for chiral MDMA analysis, and 1-1,000 ng/mL for chiral MDA analysis. Accuracy, precision, selectivity, and sensitivity of both bioanalytical methods were in accordance with regulatory guidelines. Furthermore, accuracy and precision of the enantioselective method were maintained when racemic calibrations were used to measure quality control samples containing only one of the enantiomers. Likewise, enantiomeric calibrations could be used to reliably quantify enantiomers in racemic samples. The achiral and enantioselective methods were employed to assess pharmacokinetic parameters in clinical study participants treated with racemic MDMA or one of its enantiomers. The pharmacokinetic parameters assessed with both bioanalytical methods were comparable. In conclusion, the enantioselective method is useful for the simultaneous quantification of both enantiomers in subjects treated with racemic MDMA. However, as MDMA and MDA do not undergo chiral inversion, enantioselective separation is not necessary in subjects treated with only one of the enantiomers.