Can the Intake of a Synthetic Tryptamine be Detected Only by Blood Plasma Analysis? A Clinical Toxicology Case Involving 4-HO-MET.

Tryptamines represent a group of hallucinogenic new psychoactive substances with increasing prevalence. Unfortunately, only limited data concerning their toxicology and bioanalysis is available as tryptamines are not included in routine screening procedures in many laboratories. In order to expand the current knowledge, we report a non-fatal clinical toxicology case involving the synthetic tryptamine 4-HO-MET (4-hydroxy-N-methyl-N-ethyl-tryptamine, 3-{2-[ethyl(methyl)amino]ethyl}-1H-indol-4-ol, metocin, or methylcybin). Only blood was available and our systematic blood plasma screening approaches based on gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) coupled to low-resolution linear ion trap mass spectrometry (ITMSn) or high-resolution tandem mass spectrometry (HRMS/MS) were conducted. The ingestion of the synthetic tryptamine 4-HO-MET could be revealed by blood plasma analysis using both LC-based systematic screening approaches, but not using GC-MS. Furthermore, the detection of metabolites, which may be used to confirm an intake of the parent compound 4-HO-MET, was only successful using LC-HRMS/MS most probably due to its increased sensitivity compared to LC-ITMSn. A total of four metabolites were detected in blood including N-demethyl-, oxo-, and hydroxy-4-HO-MET, as well as the N-oxide. Finally, LC-HRMS/MS analysis revealed a plasma concentration of 193 ng/mL for 4-HO-MET using the standard addition method. The presented data may help clinical and forensic toxicologists with the interpretation of future cases involving synthetic tryptamines, especially if only blood samples are available.