2024-03-29T00:14:44Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/202872019-02-14T10:24:59Zcom_10261_5063com_10261_5col_10261_5066
00925njm 22002777a 4500
dc
Pizarro, Nieves
author
Llebaria, Amadeu
author
Cano, Silvia
author
Joglar Tamargo, Jesús
author
Farré, Magí
author
Segura, Jordi
author
Torre, Rafael de la
author
2003-01-06
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is consumed as the racemate but some metabolic steps are enantioselective. In addition, chiral properties are preserved during MDMA biotransformation. A quantitative analytical methodology using gas chromatography/mass spectrometry (GC/MS) to determine enantioselective disposition in the body of MDMA and its main metabolites including 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) was developed. Plasma and urine samples were collected from a male volunteer. The analysis of MDMA, MDA, and 4-hydroxy-3-methoxy metabolites by GC/MS required a two-step derivatization procedure. The first step consisted of derivatization of the amine with enantiomerically pure Mosher's reagent ((R)-MTPCl). Triethylamine was used as a base to neutralize hydrochloric acid formed during the reaction allowing quantitative derivatization, which resulted in a substantial improvement in the sensitivity of the method compared with other previously described techniques. Further treatment with ammonium hydroxide was required since both amine and hydroxyl groups underwent derivatization in the reaction. Ammonium hydroxide breaks bonds formed with hydroxyl groups without affecting amine derivatives. The second derivatization step using hexamethyldisilazane was needed for metabolites containing phenol residues. This derivatization method permitted the stereochemically specific study of MDMA and its main monohydroxylated metabolites by GC/MS. A detailed study of the chemical reactions involved in the derivatization steps was indispensable to develop a straightforward, sensitive, and reproducible method for the analysis of the parent drug compound and its metabolites.
Rapid Communications in Mass Spectrometry 17(4): 330-336 (2003)
0951-4198
http://hdl.handle.net/10261/20287
10.1002/rcm.919
1097-0231
3,4-Methylenedioxymethamphetamine
Gas chromatography-mass spectrometry
Metabolic reactions
Plasma Analysis
Urine analysis
Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites by gas chromatography/mass spectrometry