An LC–MS–MS method for quantitative analysis of six trimethoxyamphetamine designer drugs in rat plasma, and its application to a pharmacokinetic study

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.