Concentrations and Ratios of Amphetamine, Methamphetamine, MDA, MDMA, and MDEA Enantiomers Determined in Plasma Samples from Clinical Toxicology and Driving Under the Influence of Drugs Cases by GC-NICI-MS*

The pharmacological effects of amphetamine, methamphetamine, MDA, MDMA, and MDEA depend on their mirror-image molecular forms (enantiomers), which differ in how they act in the body. Analysis of plasma from clinical toxicology cases and from drivers suspected of drug impairment showed that concentrations of most enantiomers were lower in routine screening samples than in intoxication or driving-under-the-influence cases. Drivers under the influence had higher levels of both amphetamine enantiomers than intoxicated patients. Differences in the ratio of R to S enantiomers for several drugs between groups suggest these ratios can help distinguish recent from past use. In one MDMA poisoning, the R form cleared more slowly (half-life 6.0 hours) than the S form (4.1 hours), and the ratio of R to S rose over time.

Study at a glance

Abstract

Enantiomers of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) exhibit different pharmacological properties. This may be important for the interpretation of analytical results. Plasma samples were analyzed using validated negative ion chemical ionization gas chromatography-mass spectrometry procedures. The results for clinical toxicology cases, divided into screening (SCR) and intoxication (ITX) cases, and those of driving under the influence of drugs (DUID) cases were compared. The concentrations of all enantiomers, except R-(-)-MDA and R-(-)- and S-(+)-MA, in the SCR samples were lower than in ITX and DUID samples. Differences between concentrations in ITX and DUID samples were only significant for both enantiomers of AM (DUID higher). These findings suggested impairment in drugged drivers. Different enantiomer ratios (R vs. S) were found for AM between DUID and SCR samples, for MDMA between ITX and SCR samples, and for MDA between DUID and ITX and DUID and SCR samples. Higher MDMA enantiomer ratios in SCR compared to ITX samples are in accordance with a previously described increase of those ratios over time, possibly allowing differentiation of recent from nonrecent ingestion. Pharmacokinetic analysis of a MDMA poisoning yielded elimination half-lives of 6.0 h for R-(-)-MDMA and 4.1 h for S-(+)-MDMA. The enantiomer ratios rose exponentially over time.