Trimethoxyamphetamine

Abstract: A reliable and accurate GC-MS method was developed that allows both mass spectrometric and chromatographic discrimination of the six aromatic positional isomers of trimethoxyamphetamine (TMA). Regardless of the trifluoroacetyl (TFA) derivatization, chromatographic separation of all the investigated isomers was achieved by using DB-5 ms capillary columns (30 m x 0.32 mm i.d.), with run times less than 15 min. However, the mass spectra of the nonderivatized TMAs, except 2,4,6-trimethoxyamphetmine (TMA-6), showed insufficient difference for unambiguous discrimination. On the other hand, the mass spectra of the TFA derivatives of the six isomers exhibited fragments with significant intensity differences, which allowed the unequivocal identification of all the aromatic positional isomers investigated in the present study. This GC-MS technique in combination with TFA derivatization, therefore, is a powerful method to discriminate these isomers, especially useful to distinguish the currently controlled 3,4,5-trimethoxyamphetmine (TMA-1) and 2,4,5-trimethoxyamphetmine (TMA-2) from other uncontrolled TMAs.

Abstract: Trimethoxyamphetamines (TMAs) comprise a family of hallucinogenic drugs that includes various different positional isomers, which are important both for their hallucinogenic activity and their circulation in illicit drug markets. This report describes a method for identification and quantitation of six TMA isomers in rat plasma by solid-phase extraction and liquid chromatography–tandem mass spectrometry (LC–MS–MS) with electrospray ionization. Mescaline-d 1 was used as internal standard. Multiple reaction monitoring on a triple quadrupole mass spectrometer operating in the positive ion mode was used for detection. The chromatographic system used a Varian Polaris C18-A column (2.0 × 100 mm i.d., 3 μm) and gradient elution with acetonitrile and 0.1 % formic acid in water. The calibration curves were linear over the concentration range from 10 to 200 ng/ml for all drugs with correlation coefficients that exceeded 0.998. The limits of detection and quantitation ranged from 1.1 to 2.3 ng/ml and from 6.9 to 10.2 ng/ml, respectively. The validation data, such as precision, accuracy, and recovery, showed good reproducibility and selectivity. This method was successfully applied to evaluating the pharmacokinetic profiles of TMAs in rats.

Abstract: Analytical profiles (Marquis color testing, infrared spectroscopy, nuclear magnetic resonance, thin layer chromatography, high-performance liquid chromatography, and gas chromatography/mass spectrometry) are presented for 3,4,5-trimethoxyamphetamine, 2,4,5-trimethoxyamphetamine, and 2,4,6-trimethoxyamphetamine. The data allows identification and differentiation of these positional isomers.