Top

Published in:

01-01-2014 | Original Article

Metabolism of the newly encountered designer drug α-pyrrolidinovalerophenone in humans: identification and quantitation of urinary metabolites

Authors: Noriaki Shima, Munehiro Katagi, Hiroe Kamata, Shuntaro Matsuta, Keiko Sasaki, Tohru Kamata, Hiroshi Nishioka, Akihiro Miki, Michiaki Tatsuno, Kei Zaitsu, Akira Ishii, Takako Sato, Hitoshi Tsuchihashi, Koichi Suzuki

Published in: Forensic Toxicology | Issue 1/2014

Abstract

Urinary metabolites of α-pyrrolidinovalerophenone (α-PVP) in humans were investigated by analyzing urine specimens obtained from abusers. Unambiguous identification and accurate quantification of major metabolites were realized using gas chromatography–mass spectrometry and liquid chromatography-tandem mass spectrometry with newly synthesized authentic standards. Two major metabolic pathways were revealed: (1) the reduction of the β-keto moiety to 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-ol (OH-α-PVP, diastereomers) partly followed by conjugation to its glucuronide, and (2) the oxidation at the 2″-position of the pyrrolidine ring to α-(2″-oxo-pyrrolidino)valerophenone (2″-oxo-α-PVP) via the putative intermediate α-(2″-hydroxypyrrolidino)valerophenone (2″-OH-α-PVP). Of the metabolites retaining the structural characteristics of the parent drug, OH-α-PVP was most abundant in most of the specimens examined.

Sauer S, Peters FT, Haas C, Meyer MR, Fritschi G, Maurer HH (2009) New designer drug α-pyrrolidinovalerophenone (PVP): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. J Mass Spectrom 44:952–964PubMedCrossRef

Shin H-S, Shin Y-SO, Lee S, Park B–B (1996) Detection and identification of pyrovalerone and its hydroxylated metabolite in the rat. J Anal Toxicol 20:568–572PubMedCrossRef

Jane MP, Lewis SN (2012) The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol 8:33–42CrossRef

Meyer MR, Du P, Schuster F, Maurer HH (2010) Studies on the metabolism of the α-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC–MS and LC-high resolution MS and its detectability in urine by GC–MS. J Mass Spectrom 45:1426–1442PubMedCrossRef

Springer D, Fritschi G, Maurer HH (2002) Metabolism and toxicological detection of the new designer drug 4′-methyl-alpha-pyrrolidinopropiophenone in urine using gas chromatography-mass spectrometry. J Chromatogr B 773:25–33CrossRef

Springer D, Fritschi G, Maurer HH (2003) Metabolism of the new designer drug 3′,4′-methylenedioxy-alpha-pyrrolidinopropiophenone studied in urine using gas chromatography–mass spectrometry. J Chromatogr B 793:377–388CrossRef

Meltzer PC, Butler D, Deschamps JR, Madras BK (2006) 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogs: a promising class of monoamine uptake inhibitors. J Med Chem 49:1420–1432PubMedCentralPubMedCrossRef

Ammann D, McLaren JM, Gerostamoulos D, Beyer J (2012) Detection and quantification of new designer drugs in human blood: part 2—designer cathinones. J Anal Toxicol 36:381–389PubMedCrossRef

Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2013) Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012. Forensic Toxicol 31:44–53CrossRef

10.

Namera A, Nakamoto A, Saito T, Nagao M (2011) Colorimetric detection and chromatographic analyses of designer drugs in biological materials: a comprehensive review. Forensic Toxicol 29:1–24CrossRef

11.

Namera A, Urabe S, Saito T, Torikoshi-Hatano A, Shiraishi H, Arima Y, Nagao M (2013) A fatal case of 3,4-methylenedioxypyrovalerone poisoning: coexistence of α-pyrrolidinobutiophenone and α-pyrrolidinovalerophenone in blood and/or hair. Forensic Toxicol 31:338–343CrossRef

12.

Saito T, Namera A, Osawa M, Aoki H, Inokuchi S (2013) SPME–GC–MS analysis of α-pyrrolidinovalerophenone in blood in a fatal poisoning case 31:328–332CrossRef

13.

Kamata HT, Shima N, Zaitsu K, Kamata T, Miki A, Nishikawa M, Katagi M, Tsuchihashi H (2006) Metabolism of the recently encountered designer drug, methylone, in humans and rats. Xenobiotica 36:709–723PubMedCrossRef

14.

Zaitsu K, Katagi M, Kamata HT, Kamata T, Shima N, Miki A, Tsuchihashi H, Mori Y (2009) Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. Forensic Sci Int 188:131–139PubMedCrossRef

15.

Zaitsu K, Katagi M, Tatsuno M, Sato T, Tsuchihashi H, Suzuki K (2011) Recently abused β-keto derivates of 3,4-methylenedioxyphenylalkylamines: a review of their metabolisms and toxicological analysis. Forensic Toxicol 29:73–84CrossRef

16.

Shima N, Katagi M, Kamata H, Matsuta S, Nakanishi K, Zaitsu K, Kamata T, Nishioka H, Miki A, Tatsuno M, Sato T, Tsuchihashi H, Suzuki K (2013) Urinary excretion and metabolism of the newly encountered designer drug 3,4-dimethylmethcathinone in humans. Forensic Toxicol 31:101–112CrossRef

17.

Meyer MR, Wilhelm J, Peters FT, Maurer HH (2010) Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem 397:1225–1233PubMedCrossRef

18.

Morita M, Ando H (1983) Analysis of methamphetamine and its metabolites in urine from a habitual user of the stimulant (in Japanese with English abstract). Eisei Kagaku 29:318–322CrossRef

19.

Imamura Y, Kojima Y, Higuchi T, Akita H, Oishi T, Otagiri M (1989) Stereoselective reduction of acetohexamide in cytosol of rabbit liver. J Pharmacobiodyn 12:731–735PubMedCrossRef

20.

Kobana K, Watanabe K, Kimura T, Matsunaga T, Kondo S, Yamamoto I (2000) A carbonyl reductase-catalyzing reduction of N ³-phenacyluridine in rabbit liver. Biol Pharm Bull 23:917–921PubMedCrossRef

21.

Hukkanen J, Jacob P III, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79–115PubMedCrossRef

22.

Brenneisen R, Geisshüsler S, Schorno X (1986) Metabolism of cathinone to (−)-norephedrine and (−)-norpseudoephedrine. J Pharm Pharmacol 38:298–300PubMedCrossRef

Title: Metabolism of the newly encountered designer drug α-pyrrolidinovalerophenone in humans: identification and quantitation of urinary metabolites
Authors: Noriaki Shima
Munehiro Katagi
Hiroe Kamata
Shuntaro Matsuta
Keiko Sasaki
Tohru Kamata
Hiroshi Nishioka
Akihiro Miki
Michiaki Tatsuno
Kei Zaitsu
Akira Ishii
Takako Sato
Hitoshi Tsuchihashi
Koichi Suzuki
Publication date: 01-01-2014
Publisher: Springer Japan
Published in: Forensic Toxicology / Issue 1/2014
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-013-0202-9

At a glance: The STEP trials

Springer Medicine

Metabolism of the newly encountered designer drug α-pyrrolidinovalerophenone in humans: identification and quantitation of urinary metabolites

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

MALDI-TOF mass spectrometric determination of four pyrrolidino cathinones in human blood

Occurrence of postmortem production of ethylene glycol and propylene glycol in human specimens

Homicide–suicide by oral administration of cyclobarbital

Presence of appreciable amounts of ethylene glycol, propylene glycol, and diethylene glycol in human urine of healthy subjects

Simultaneous determination of tryptamine analogues in designer drugs using gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry

Rapid and simultaneous extraction of acidic and basic drugs from human whole blood for reliable semi-quantitative NAGINATA drug screening by GC–MS