New designer drug 1‐(3‐trifluoromethylphenyl) piperazine (TFMPP): gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry studies on its phase I and II metabolism and on its toxicological detection in rat urine

Abstract

Studies are described on the phase I and II metabolism and the toxicological analysis of the piperazine-derived designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rat urine using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). The identified metabolites indicated that TFMPP was extensively metabolized, mainly by hydroxylation of the aromatic ring and by degradation of the piperazine moiety to N-(3-trifluoromethylphenyl)ethylenediamine, N-(hydroxy-3-trifluoromethylphenyl)ethylenediamine, 3-trifluoromethylaniline, and hydroxy-3-trifluoromethylaniline. Phase II reactions included glucuronidation, sulfatation and acetylation of phase I metabolites. 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 TFMPP and its above-mentioned metabolites in rat urine after single administration of a dose calculated from the doses commonly taken by drug users. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of TFMPP in human urine.

Investigation of the First Deaths in the United Kingdom Involving the Detection and Quantitation of the Piperazines BZP and 3-TFMPP

“…The published literature presents analytical data for various piperazines (in particular BZP, TFMPP, and CPP) relating to immunoassay, gas chromatography (GC)-MS (derivatized and underivatized), and GC with nitrogen-phosphorus detection (NPD) (1,5,7,(23)(24)(25)(26)(27). There have only been limited HPLC-UV (UV maxima only) and LC-MS data shown (1,(26)(27)(28).…”

Influence du cytochrome P450 2D6 sur le métabolisme de la TFMPP (1-(3-trifluoro-méthylphenyl) pipérazine) : étude à l'aide de modèles in vitro et in vivo

“…Metabolism studies of new designer drugs are commonly conducted using rat models, due to ethical reservation about human studies (3,(18)(19)(20)(21) For confirmation, the human hepatic CYPs involved in TFMPP hydroxylation were identified using microsomal preparations from different sources. This method has already been described for other new designer drugs (11;16).…”

“…The involvement of particular cytochrome P450 (CYP) in the biotransformation of a new drug is needed for risk assessment. Previous in vivo studies in male Wistar rats (WI) showed that TFMPP was mainly metabolized by aromatic hydroxylation to hydroxy TFMPP (HO-TFMPP) ( Figure 1) followed by partial glucuronidation or sulfatation (3). The first aim of the work presented here was to study, whether TFMPP hydroxylation may also be catalyzed by polymorphically expressed CYP2D6.…”

Metabolism of designer drugs. Piperazine derivatives

“…В большинстве стран мира (кроме Нидерландов) он вклю-чен в списки контролируемых субстанций. Описан метабо-лизм TFMPP в опытах на крысах [24]. Авторы идентифи-цировали метаболиты, используя ГХ МС с электронным ударом и ВЭЖХ МС с ионизацией электроспреем.…”

“…Дальнейшая био-трансформация приводит к замещенным анилинам (5 и 6), и при участии N-ацетилтрансферазы анилины ацети-лируются (метаболиты 7 и 8). Кроме описанных ранее [24] метаболитов, в моче потребителей TFMPP идентифици-рованы метаболиты, гидроксилированные по пипериди-новому кольцу и этилендиаминовому фрагменту (метабо-литы 9 и 10). Нативный TFMPP выделяется с мочой в ко-личестве менее 10%.…”