New designer drug 4‐iodo‐2,5‐dimethoxy‐β‐phenethylamine (2C‐I): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric and capillary electrophoretic/mass spectrometric techniques

Abstract

Studies are described on the metabolism and the toxicological analysis of the phenethylamine-derived designer drug 4-iodo-2,5-dimethoxy-beta-phenethylamine (2C-I) in rat urine using gas chromatographic/mass spectrometric (GC/MS) techniques, and for a particular question, using capillary electrophoretic/mass spectrometric (CE/MS) techniques. The identified metabolites indicated that 2C-I was metabolized on the one hand by O-demethylation in position 2 and 5, respectively, followed either by N-acetylation or by deamination with subsequent oxidation to the corresponding acid or reduction to the corresponding alcohol, respectively. The latter metabolite was hydroxylated in beta-position and further oxidized to the corresponding oxo metabolite. On the other hand, 2C-I was metabolized by deamination with subsequent oxidation to the corresponding acid or reduction to the corresponding alcohol, respectively. 2C-I and most of its metabolites were partially excreted in conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of an intake of a dose of 2C-I in rat urine that corresponds to a common drug users' dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-I in human urine.

Recurrent Seizures and Serotonin Syndrome Following “2C-I” Ingestion

“…Because of rapid metabolism, beta phenethylamine itself is not commonly abused, but the addition of a hydrophobic R group in position 4, along with methoxy groups in positions 2 and 5 make a more stable compound. Collectively, this group of drugs is referred to as the "2C" drugs [3]. As a class, these drugs, including 2C-I, have demonstrated agonism at the 5HT 2 receptor, which is believed to be the etiology of the hallucinogenic properties [1,4].…”

2C or Not 2C: Phenethylamine Designer Drug Review

“…The compound is deaminated and then oxidated to either the corresponding acid or base [18,20,21]. MAO-A and MAO-B are the major enzymes involved in the deamination of 2Cs [22].…”

“…MAO-A and MAO-B are the major enzymes involved in the deamination of 2Cs [22]. Studied 2Cs have a greater affinity for MAO-A versus MAO-B; MAO-A has a larger binding pocket and can accommodate larger substituents at the 4 position on the phenyl ring [21][22][23]. Due to the involvement of MAOs in 2C metabolism, there are potential drug-drug interactions with monoamine oxidase inhibitors, which can increase serum 2C concentrations and increase risk for 2C toxicity [22].…”

Designer drugs: aspectos analíticos e biológicos

“…Para algumas 2Cs estão disponíveis métodos para screening e para quantificação em amostras de plasma e urina, [43][44][45] sendo que as técnicas analíticas empregadas são CG/EM, cromatografia gasosa com detector de nitrogênio e fósforo (CG/ DNF) 46 e eletroforese capilar acoplada à espectrometria de massas (EC/EM). 47,48 Por outro lado, em 2004, foi apresentado um método utilizando a CG/EM para a detecção de compostos 2C na urina. No entanto, para a análise toxicológica, principalmente na urina, é importante conhecer previamente as reações de biotransformação dos compostos, especialmente se eles são excretados inalterados ou na forma de metabólitos.…”