Fast and Robust Ultra‐High‐Performance Liquid Chromatography Analysis of Thermally Labile Psychoactive Phenethylamines

ABSTRACT We report the first ultra‐high‐performance liquid chromatography (UHPLC) coupled with a diode array detection method for the rapid, sensitive, and reliable quantification of new psychoactive substances, including 2,5‐dimethoxyphenethylamines, N‐(2‐hydroxybenzyl)‐2,5‐dimethoxyphenethylamines, and N‐(2‐methoxybenzyl)‐2,5‐dimethoxyphenethylamines. In these compounds, the R group represents a substitution at the 4‐position of the phenethylamine ring, such as a halogen or an ethyl group. This analytical approach overcomes the limitations caused by the thermal lability of these analytes in gas chromatography combined with mass spectrometry (MS) and in HPLC combined with tandem MS. The method was validated over the range of 200–25,000 ng/mL, with intra and inter‐assay relative standard deviation values ≤6%. The limit of detection for the compounds was 0.05 µg/mL, except for 2‐(((4‐chloro‐2,5‐dimethoxyphenethyl)amino)methyl)phenol (0.1 µg/mL). The limit of quantification was 0.2 µg/mL, with a total run time of 8 min per analysis. The method was successfully applied to 156 real‐world blotter samples, providing unmatched speed and precision for forensic laboratories.