Drug Testing in Blood: Validated Negative-Ion Chemical Ionization Gas Chromatographic–Mass Spectrometric Assay for Enantioselective Measurement of the Designer Drugs MDEA, MDMA, and MDA and Its Application to Samples from a Controlled Study with MDMA

Abstract

Background:The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. Methods: The analytes were extracted from <0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S-(؊)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered. Results: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was

The Role of Human Hepatic Cytochrome P450 Isozymes in the Metabolism of Racemic 3,4-Methylenedioxy-Methamphetamine and Its Enantiomers

“…The separation of the MDA enantiomers was comparable with that described by Peters et al (2005). The mass fragmentograms shown in Fig.…”

“…2, B and C, purity check of the isolated enantiomers by GC-MS indicated high optical purities of S-MDMA-HCl (97%) and R-MDMA-HCl (98%), respectively. The elution order was confirmed according to (Peters et al, 2005). The yield was approximately 60% or 12 mg/enantiomer.…”

“…The compounds were eluted twice with 10 ml of freshly prepared mixture of methanol/aqueous ammonia [96:4 (v/v)]. The eluates were evaporated to dryness under reduced pressure and reconstituted in 1.0 ml of 0.01 M HCl and quantified according to Peters et al (2005).…”

“…Derivatization was performed according to (Peters et al, 2005), with slight modifications. After adding 20 l of derivatization reagent (0.1 mol/l S-heptafluorobutyrylprolyl chloride in dichloromethane), the reaction vials were sealed and left on a rotary shaker at ambient temperature for 30 min.…”

“…They also differ in their dose-response curves for changes in serotonergic function and neurotoxicity, and their in vivo kinetics are known to be different. It has been shown that after ingestion of racemic MDMA, the S-enantiomer is eliminated at a higher rate than the R-enantiomer (Fallon et al, 1999;Kalant, 2001;Kraemer and Maurer, 2002;Peters et al, 2003Peters et al, , 2005Pizarro et al, 2004). Enantioselective metabolism is the most likely explanation for the enantioselective pharmacokinetics of MDMA.…”