The in vivo and in vitro metabolism and the detectability in urine of 3’,4’‐methylenedioxy‐alpha‐pyrrolidinobutyrophenone (MDPBP), a new pyrrolidinophenone‐type designer drug, studied by GC‐MS and LC‐MSⁿ

Abstract

3',4'-Methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP), a designer drug of the pyrrolidinophenone-type, was first seized in Germany in 2009. It was also identified in 'legal high' samples investigated in the UK. Therefore, the aim of the presented work was to identify its in vivo and in vitro phase I and II metabolites using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-ion trap mass spectrometry (LC-MS(n) ). Furthermore, detectability of MDPBP in rat and human urine using standard urine screening approaches (SUSA) by GC-MS and LC-MS(n) was studied. The metabolites were isolated either directly or after enzymatic cleavage of conjugates by solid-phase extraction (C18, HCX). The metabolites were then analyzed and structures proposed after GC-MS (phase I) and LC-MS(n) (phase II). Based on these identified metabolites, the following main metabolic steps could be proposed: demethylenation followed by methylation of one hydroxy group, aromatic and side chain hydroxylation, oxidation of the pyrrolidine ring to the corresponding lactam as well as ring opening to the corresponding carboxylic acid. Furthermore, in rat urine after a typical user's dose as well as in human urine, mainly the metabolites could be detected using the authors' SUSA by GC-MS and LC-MS(n) . Thus, it should be possible to monitor an application of MDPBP assuming similar toxicokinetics in humans. Finally, CYP2C19 and CYP2D6 could be identified as the isoenzymes mainly responsible for demethylenation.

Urinary excretion and metabolism of the α-pyrrolidinophenone designer drug 1-phenyl-2-(pyrrolidin-1-yl)octan-1-one (PV9) in humans

“…In particular, a-pyrrolidinophenones, including 3,4-methylenedioxypyrovalerone (MDPV) [6,7], apyrrolidinovalerophenone (a-PVP) [8][9][10][11][12][13], a-pyrrolidinobutiophenone (a-PBP) [13][14][15], 4-methyl-a-pyrrolidinohexanophenone (MPHP) [16,17], and 3,4-methylenedioxya-pyrrolidinobutiophenone (MDPBP) [18], have rapidly become a popular class of designer drugs. 1-Phenyl-2-(pyrrolidin-1-yl)octan-1-one (PV9) is an a-PVP analog in which the alkyl chain is elongated up to eight carbons, also known as a-pyrrolidinooctanophenone (a-POP).…”

Identification of phase I and II metabolites of the new designer drug α‐pyrrolidinohexiophenone (α‐PHP) in human urine by liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS)

“…They are chemical derivatives of cathinone, a stimulating alkaloid of the plant khat ( Catha edulis ), in which the amino group has been substituted by a pyrrolidine rest instead. Many derivatives of α ‐pyrrolidinophenones have been already described in literature: Pyrovalerone, methylenedioxypyrovalerone (MDPV), α‐pyrrolidinopropiophenone (α‐PPP), 4′‐methyl‐ α ‐pyrrolidinopropiophenone (MPPP), 3′,4′‐methylenedioxy‐ α ‐pyrrolidinobutyrophenone (MDPBP), 4′‐methyl‐ α ‐pyrrolidinohexanophenone (MPHP) and a lot more . They are highly potent and selective dopamine and noradrenaline transporter inhibitors, and various derivatives have been synthesised and tested in vitro .…”

“…Metabolic profiles of them are studied extensively by many research groups. The working group of Prof. Maurer (Saarland University, Germany), for example, routinely delivers data for NPS, including pyrrolidinophenones, by monitoring their metabolites obtained from incubations with human liver microsomes, the urine of rats and real‐case intoxication samples . Shima et al .…”

Evolution of new narcotic substances and methods of their determination

“…These advantages along with the long presence of NSs and their metabolites in urine and the possibility of using a quite available method of analysis (GC-MS) make it convenient for the determination of narcotic substances [47,48]. A significant drawback of urine is that only part of NSs (usually most hydrophilic sub stances [172]) are excreted in an invariable state, while a considerable amount of cathinones [173][174][175][176][177][178][179][180][181] and all synthetic cannabimimetics are metabolized. The presence of initial substances in urine for the last named substances (except for benzoylindole derivative AM 2233) is practically excluded.…”