Chromatographic and Mass Spectral Methods of Identification for the Side-Chain and Ring Regioisomers of Methylenedioxymethamphetamine

Abstract

The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) is one of a total of 10 regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines of MW 193 that yields regioisomeric fragment ions with equivalent mass (m/z 58 and 135/136) in the electron-impact (EI) mass spectrum. Thus, these 10 methylenedioxyphenethylamines are uniquely isomeric; they have the same molecular weight and equivalent major fragments in their mass spectra. The specific identification of one of these compounds (i.e., Ecstasy or 3,4-MDMA) in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This study reports the synthesis, chemical properties, spectral characterization, and chromatographic analysis of these 10 unique regioisomers. The ten 2,3- and 3,4-regioisomers of MDMA are synthesized from commercially available precursor chemicals. In the EI mass spectra, the side-chain regioisomers show some variation in the relative intensity of the major ions, with the exception of only one or two minor ions that might be considered side-chain specific fragments. The position of substitution for the methylenedioxy ring is not easily determined by mass spectral techniques, and the ultimate identification of any one of these amines with the elimination of the other nine must depend heavily upon chromatographic methods. The chromatographic separation of these 10 uniquely regioisomeric amines are studied using reversed-phase liquid chromatographic methods with gradient elution and gas chromatographic techniques with temperature program optimization.

Differentiation of methoxybenzoylpiperazines (OMeBzPs) and methylenedioxybenzylpiperazines (MDBPs) By GC‐IRD and GC‐MS

“…The starting materials for compounds 1, 2, and 3 are 2, 3 and 4‐methoxy benzoylchloride, respectively and the starting material for compound 5 is 3,4‐ methylenedioxybenzaldehyde (piperonal), and all are commercially available. 2,3‐methylenedioxybenzaldehyde is the starting material for 2,3‐MDBP (compound 4) and its preparation has been previously reported . All laboratory reagents and solvents were obtained from Aldrich Chemical Co. (Milwaukee, WI, USA) or Fisher Scientific (Atlanta, GA, USA).…”

Differentiation of methylenedioxybenzylpiperazines (MDBPs) and methoxymethylbenzylpiperazines (MMBPs) By GC-IRD and GC–MS

“…The starting materials for compounds 3 and 6 are 4-methoxy-3-methyl benzaldehyde and 3,4-methylenedioxybenzaldehyde (piperonal), respectively and both are commercially available. 2,3-Methylenedioxybenzaldehyde is the starting material for 2,3-MDBP and its preparation has been previously reported [24,25]. The starting aldehyde for compound 4 was prepared from the corresponding 3-methoxy-4-methyl benzoic acid methyl ester (TCI, Tokyo, Japan) by reduction using sodium bis(2-methoxyethoxy) aluminium hydride (Red-Al) followed by oxidizing the resulting alcohol using pyridinium chlorochromate (PCC).…”

Differentiation of methylenedioxybenzylpiperazines (MDBP) by GC–IRD and GC–MS

“…The preparation of 2,3-methylenedioxybenzaldehyde has been reported previously [21,22]. The two regioisomers were prepared by the reductive amination of the appropriate aldehyde and piperazine in presence of sodium cyanoborohydride.…”