1 INTRODUCTION

Originally, phenethylamines and their derivatives, such as [2‐(4‐iodo‐2,5‐dimethoxyphenyl)‐N‐[(2‐methoxyphenyl)methyl]ethylamine] (25I‐NBOMe), were developed for pharmacological studies on the 5‐HT 2A receptor and for positron emission tomography (PET) imaging, respectively.1-3 Their rising popularity since 2010 as designer drugs of abuse can be traced back to the much lower costs of synthesis but similar effects compared with the better known hallucinogenic compound lysergic acid diethylamide (LSD).4-6 LSD and NBOMe derivatives as well, are highly potent ligands and partial agonists at the 5‐HT 2A ‐receptor, which induces the typical and desired effects of these drugs.7-9 For NBOMe compounds, effects such as stimulation, euphoria, changes in consciousness and hallucinations are described.10-13 Hence, drug producers and dealers sell them as a replacement for LSD, or misleadingly as LSD itself.14-16

Because of the similar effects and the low effective doses of LSD and NBOMes, unintentional effects of NBOMes by consumers may occur. Besides the reported clinical effects such as tachycardia, hypertension, agitation, and aggression, toxicological issues have to be considered as well.17 Maurer et al. showed an extensive metabolism of 25I‐NBOMe, nevertheless, they claim a lack of systematic studies on the metabolism of NBOMe derivatives.18, 19

As already described in many cases, NBOMe consumption may lead to severe health problems or even death, caused by an overdose.20-23 To assess the risk of overdose incidents, blotter papers have to be investigated in more detail. NBOMes often are sold on perforated blotter sheets, from which small rectangles, the so‐called “trips”, can be torn off. One common manufacturing process is the immersion of “empty” blotter paper into a drug solution and subsequent dry hanging. The amount of NBOMes on a single trip ranges from approximately 500 to 1500 μg, while the single effective dose for an unexperienced user is around 100 μg.24 Coelho et al. used direct ATR‐FTIR spectroscopy for rapid detection of NBOMes on blotter papers, which required no sample preparation and was directly applied on blotter papers. The data indicated a heterogeneous distribution of the NBOMes.25 Furthermore, the infrared spectra showed the presence of a plastic polymer on the front side of the blotter papers.

A blotter sheet, seized by the German police, containing approximately 20 “trips”, was analyzed by three different imaging techniques. These 2D analyses will reveal a possible heterogeneous appearance of NBOMes in some areas of the blotter paper, which could lead to overdose incidents if these hotspots are torn off. First, rapid and non‐destructive analysis of the elemental distribution was performed by means of micro‐X‐ray fluorescence (μXRF) spectroscopy and was subsequently supported by matrix assisted laser desorption ionization (MALDI)‐mass spectrometry (MS) for molecular imaging. Additionally, imaging utilizing laser ablation (LA)‐inductively coupled plasma (ICP)‐optical emission spectroscopy (OES) was performed for 3D analysis since LA enables the acquisition of a depth profile. The obtained imaging results were then confirmed via high performance liquid chromatography (HPLC)‐MS as a complementary technique.