Characterization of 2C-phenethylamines using high-resolution mass spectrometry and Kendrick mass defect filters

Abstract The identification of synthetic designer drugs is challenging due to the high degree of structural similarity among compounds within a given class. In efforts to circumvent current legislation, new designer drug analogs that appear on the market have the same core structure as a regulated compound but differ only in the position or the identity of a single substituent. Reference standards of the new analogs are not immediately available for comparison, making identification using conventional gas chromatography-mass spectrometry (GC-MS) methods more challenging. In this work, the potential of mass defect to characterize compounds according to structural subclass was investigated. This initial work focused on synthetic phenethylamines, with the development of mass defect filters to characterize compounds as 2,5-dimethoxy-phenethylamines (2C-phenethylamines). Three sets of phenethylamines, including 2C-, aminopropylbenzofuran (APB-), and 2,5-dimethoxy- N -(2-methoxybenzyl) (NBOMe-) phenethylamines, were analyzed by GC-time-of-flight mass spectrometry (GC-TOFMS), using different instruments and under different conditions. The resulting accurate mass data were used to develop Kendrick mass defect filters based on the molecular ion and common neutral losses observed in a training set of 2C-phenethylamines. Successful characterization of test set compounds as 2C-phenethylamines with distinction from other structurally similar phenethylamines was demonstrated using the molecular ion and neutral loss mass defect filters.