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

A non-fatal clinical case involving the synthetic tryptamine 4-HO-MET (metocin or methylcybin) was analyzed using blood plasma. Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS-MS) detected the parent compound and four metabolites—N-demethyl-, oxo-, hydroxy-4-HO-MET, and the N-oxide—while gas chromatography-mass spectrometry did not detect it. The plasma concentration of 4-HO-MET was 193 ng/mL. These findings provide data for clinical and forensic toxicologists interpreting future cases involving synthetic tryptamines, particularly when only blood samples are available.

Study at a glance

Abstract

Tryptamines represent a group of hallucinogenic new psychoactive substances with increasing prevalence. Unfortunately, only limited data concerning their toxicology and bioanalysis are 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). As only blood of the intoxicated patient was available, 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. However, 4-HO-MET was not detected by 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.