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

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Abstract

1-Phenyl-2-(pyrrolidin-1-yl)octan-1-one (PV9) and 16 metabolites, including diastereomers and conjugates, were identified or tentatively detected in human urine by gas chromatography–mass spectrometry and liquid chromatography–high-resolution tandem mass spectrometry. These urinary metabolites indicated that the metabolic pathways of PV9 include: (1) the reduction of ketone groups to their corresponding alcohols; (2) oxidation of the pyrrolidine ring to the corresponding pyrrolidone; (3) aliphatic oxidation of the terminal carbon atom to the corresponding carboxylate form, possibly through an alcohol intermediate (not detected); and (4) hydroxylation at the penultimate carbon atom to the corresponding alcohols followed by further oxidation to ketones, and combinations of these steps. In addition, results from the quantitative analyses of five phase-I metabolites using newly synthesized authentic standards suggested that the main metabolic pathway includes the aliphatic oxidation of terminal and/or penultimate carbons. Human metabolism of PV9 differed significantly from those of α-pyrrolidinovalerophenone and α-pyrrolidinobutiophenone, suggesting that the main metabolic pathways of α-pyrrolidinophenones significantly change depending on the alkyl chain length of the parent molecule.

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Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

Ethical approval

Informed consent was obtained from all healthy individuals included in the study, who supplied several 10 ml each of urine as blank matrix.

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Authors and Affiliations

  1. Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18 Hommachi, Chuo-ku, Osaka, 541-0053, Japan

    Noriaki Shima, Hidenao Kakehashi, Shuntaro Matsuta, Hiroe Kamata, Shihoko Nakano, Keiko Sasaki, Tooru Kamata, Hiroshi Nishioka, Akihiro Miki & Munehiro Katagi

  2. Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kei Zaitsu

  3. Division of Preventive and Social Medicine, Department of Legal Medicine, Osaka Medical College, Takatsuki, Japan

    Takako Sato & Hitoshi Tsuchihashi

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  1. Noriaki Shima
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  2. Hidenao Kakehashi
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  9. Kei Zaitsu
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Correspondence to Noriaki Shima.

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Shima, N., Kakehashi, H., Matsuta, S. et al. 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 (2015). https://doi.org/10.1007/s11419-015-0274-9

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  • DOI: https://doi.org/10.1007/s11419-015-0274-9

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