The online version of this article (https://doi.org/10.1007/s11419-018-0428-7) contains supplementary material, which is available to authorized users.
This study aims to investigate the urinary metabolites of two common α-pyrrolidinophenones (PPs), α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinoheptanophenone (α-PHPP). This report also aims to discuss the effects of alkyl chain lengths on the metabolism of PPs.
Urinary metabolites of α-PHP and α-PHPP have been investigated by analyzing urine samples from their users (n = 13 each) by liquid chromatography–high-resolution tandem mass spectrometry using reference standards of the metabolites synthesized in our laboratory.
For both drugs, metabolites via reduction of the keto moiety (1-OH metabolites) and via oxidation of the pyrrolidine ring (2″-oxo metabolites) were identified, and those via oxidation of the terminal (ω) or penultimate (ω-1) positions of the alkyl chain were tentatively identified. Quantitative analysis indicated oxidation of the pyrrolidine ring to be the major metabolic pathway for α-PHP (side chain R: hexyl), but ω or ω-1 oxidation was the major metabolic pathway for α-PHPP (R: heptyl). Comparison of their metabolic profiles with those of analogs with a longer or shorter side chain (studied previously for R: butyl, pentyl, and octyl) revealed that the alkyl chain length strongly influences the metabolic pathway. In addition, to the best of our knowledge, this is the first report describing the quantification of metabolites of α-PHP and α-PHPP in authentic urine specimens collected from the users using their reference standards synthesized.
Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (2012) The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsycopharmacology 37:1192–1203 CrossRef
Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (2013) Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsycopharmacology 38:552–562 CrossRef
Kakizaki A, Tanaka S, Numazawa S (2014) New recreational drug 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) activates central nervous system via dopaminergic neuron. J Toxicol Sci 39:1–6 CrossRef
Matsuta S, Katagi M, Nishioka H, Kamata H, Sasaki K, Shima N, Kamata T, Miki A, Tatsuno M, Zaitsu K, Tsuboi K, Tsuchihashi H, Suzuki K (2014) Structural characterization of cathinone-type designer drugs by EI mass spectrometry (in Japanese with English abstract). Jpn J Forensic Sci Technol 19:77–89 CrossRef
Matsuta S, Kakehashi H, Nakano S, Shima N, Kamata T, Nishioka H, Miki A, Sakamoto Y, Miyagawa H, Kusano M, Zaitsu K, Tsuchihashi H, Katagi M (2017) Comprehensive analysis and structural estimation of synthetic cathinones using GC–MS/MS (in Japanese with English abstract). Jpn J Forensic Sci Technol 22:109–121 CrossRef
Waters B, Ikematsu N, Hara K, Fujii H, Tokuyasu T, Tanaka M, Matsusue A, Kashiwagi M, Kubo S (2016) GC–PCI–MS/MS and LC–ESI–MS/MS databases for the detection of 104 psychotropic compounds (synthetic cannabinoids, synthetic cathinones, phenethylamine derivatives). Leg Med 20:1–7 CrossRef
Sugie K, Akutsu M, Saito K (2016) Quantitative analysis of NPS (new psychoactive substance) containing α-PVP by direct analysis in real time (DART)-TOF-MS with micro syringe injection (in Japanese with English abstract). Bunseki Kagaku 65:439–446 CrossRef
Matsuta S, Shima N, Kamata H, Kakehashi H, Nakano S, Sasaki K, Kamata T, Nishioka H, Miki A, Katagi M, Zaitsu K, Sato T, Tsuchihashi H, Suzuki K (2015) Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: identification and quantification of the phase I metabolites in urine. Forensic Sci Int 249:181–188 CrossRefPubMed
Shima N, Katagi M, Kamata H, Matsuta S, Sasaki K, Kamata T, Nishioka H, Miki A, Tatsuno M, Zaitsu K, Ishii A, Sato T, Tsuchihashi H, Suzuki K (2014) Metabolism of the newly encountered designer drug α-pyrrolidinovalerophenone in humans: identification of urinary metabolites. Forensic Toxicol 32:59–67 CrossRef
Shima N, Kakehashi H, Matsuta S, Kamata H, Kamata T, Nishioka H, Zaitsu K, Sato T, Miki A, Katagi M, Tsuchihashi H (2015) Urinary excretion and metabolism of the α-pyrrolidinophenone designer drug 1-phenyl-2-(pyrrolidin-1-yl)octan-1-one (PV9) in humans. Forensic Toxicol 33:279–294 CrossRef
Chen X (2015) Simultaneous determination of four designer drugs and their major metabolites by liquid chromatography–mass spectrometry. J Chromatogr B 992:1–7 CrossRef
Negreira N, Erratico C, Kosjek T, van Nuijs ALN, Heath E, Neels H, Covaci A (2015) In vitro Phase I and Phase II metabolism of α-pyrrolidinovalerone (α-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol. Anal Bioanal Chem 407:5803–5816 CrossRefPubMed
Paul M, Bleicher S, Guber S, Ippisch J, Polettini A, Schultis W (2015) Identification of phase I and II metabolites of new designer drug α-pyrrrolidinohexiophenone (α-PHP) in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry (LC–QTOF-MS). J Mass Spectrom 50:1305–1317 CrossRefPubMed
- Metabolism of α-PHP and α-PHPP in humans and the effects of alkyl chain lengths on the metabolism of α-pyrrolidinophenone-type designer drugs
- Springer Japan
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