Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans

Area of Science:

• Pharmacology and Toxicology
• Analytical Chemistry
• Human Pharmacokinetics

Background:

• Understanding the pharmacokinetic profile of novel psychoactive substances like methylone is crucial for public health and forensic toxicology.
• Previous research on related compounds, such as MDMA, suggests complex, non-linear pharmacokinetic behavior.
• A validated analytical method is required to accurately quantify methylone and its metabolites in biological matrices.

Purpose of the Study:

• To characterize the human plasma pharmacokinetics of methylone and its metabolite HMMC following controlled oral administration.
• To establish a reliable LC-MS/MS method for quantifying methylone, MDMA, and their metabolites in human plasma.
• To compare the pharmacokinetic linearity of methylone with that of MDMA.

Main Methods:

• A randomized, cross-over, double-blinded, placebo-controlled study involving 12 male volunteers.
• Administration of methylone at oral doses ranging from 50 mg to 200 mg.
• Quantification of methylone, MDMA, and metabolites in 468 plasma samples using a validated LC-MS/MS method with specific internal standards.

Main Results:

• Methylone plasma concentrations increased dose-proportionally, with Cmax values ranging from 153 to 604 ng/mL and AUC0-24 values from 1042.8 to 5067.9 h·ng/mL.
• Methylone exhibited rapid kinetics with a Tmax of approximately 1.5-2 hours and a half-life (T1/2) of 5.8-6.9 hours.
• HMMC displayed faster kinetics than methylone, with significantly lower Cmax and AUC0-24 values. Methylone pharmacokinetics were linear across the studied dose range, contrasting with non-linear MDMA pharmacokinetics.

Conclusions:

• Methylone demonstrates linear pharmacokinetics in humans following oral administration of 50-200 mg.
• The developed LC-MS/MS method is suitable for quantifying methylone, MDMA, and their metabolites in human plasma.
• The linear pharmacokinetic profile of methylone differentiates it from the non-linear profile observed with MDMA.