Forensic Toxicology

, Volume 36, Issue 2, pp 506–513 | Cite as

Detection of pyrovalerone as a possible synthetic by-product of 4′-methyl-α-pyrrolidinohexanophenone and 4-methyl-α-ethylaminopentiophenone in illicit drug products

  • Takaomi Tagami
  • Takahiro Doi
  • Akihiro Takeda
  • Akiko Asada
  • Kyohei Kiyota
  • Yoshiyuki Sawabe
Short Communication



Impurity profiling is an important intelligence-gathering tool that can be used to link batches of drugs, and it provides valuable insights into manufacturing and supply trends in new psychoactive substances. In a routine analysis, we detected trace amounts of pyrovalerone in illicit drug products. In this study, we investigated the cause of pyrovalerone’s presence in the illicit drug products containing 4′-methyl-α-pyrrolidinohexanophenone (MPHP) or 4-methyl-α-ethylaminopentiophenone (4-methyl-α-EAPP).


We analyzed the compounds in illicit drug products and raw material using liquid chromatography–photodiode array detection, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry.


We detected trace amounts of pyrovalerone in four illicit drug products containing MPHP or 4-methyl-α-EAPP. In every case, the amount of pyrovalerone in the illicit drug products was much lower than that of MPHP or 4-methyl-α-EAPP. We assumed that pyrovalerone was produced unintentionally. Structurally, pyrovalerone differs from MPHP with respect to the length of the alkyl side chain, and for 4-methyl-α-EAPP, the amine at the α-position is different (it bears an ethylamine instead of pyrrolidine). Pyrovalerone is thought to be produced in two different ways, as a synthetic by-product of both MPHP and 4-methyl-α-EAPP.


We assumed that pyrovalerone was derived from an impurity in a raw material or arose from contamination during the amination process. Impurity analysis, such as that described in this study, will aid in impurity profiling of cathinones.


MPHP 4-Methyl-α-ethylaminopentiophenone Pyrovalerone By-product New psychoactive substances (NPS) 



This study was supported in part by JSPS KAKENHI Grant no. 15K08834.

Compliance with ethical standards

Conflict of interest

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

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Leffler AM, Smith PB, Armas A, Dorman FL (2014) The analytical investigation of synthetic street drugs containing cathinone analogs. Forensic Sci Int 234:50–56CrossRefPubMedGoogle Scholar
  2. 2.
    Uchiyama N, Matsuda S, Kawamura M, Kikura-Hanajiri R, Goda Y (2013) Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative α-PVT and an opioid receptor agonist AH-7921 identified in illegal products. Forensic Toxicol 31:223–240CrossRefGoogle Scholar
  3. 3.
    Uemura N, Fukaya H, Kanai C, Yoshida M, Nakajima J, Takahashi M, Suzuki J, Moriyasu T, Nakae D (2014) Identification of a synthetic cannabinoid A-836339 as a novel compound found in a product. Forensic Toxicol 32:45–50CrossRefGoogle Scholar
  4. 4.
    Zaitsu K, Katagi M, Tsuchihashi H, Ishii A (2014) Recently abused synthetic cathinones, α-pyrrolidinophenone derivatives: a review of their pharmacology, acute toxicity, and metabolism. Forensic Toxicol 32:1–8CrossRefGoogle Scholar
  5. 5.
    Zuba D, Geppert B, Sekuła K, Żaba C (2013) [1-(Tetrahydropyran-4-ylmethyl)-1H-indol-3-yl]-(2, 2, 3, 3-tetramethylcyclopropyl) methanone: a new synthetic cannabinoid identified on the drug market. Forensic Toxicol 31:281–291CrossRefGoogle Scholar
  6. 6.
    Kohyama E, Chikumoto T, Tada H, Kitaichi K, Ito K (2017) Analytical differentiation of quinolinyl- and isoquinolinyl-substituted 1-(5-fluoropentyl)-1H-indole-3-carboxylates: 5F-PB-22 and its ten isomers. Forensic Toxicol 35:56–65CrossRefPubMedGoogle Scholar
  7. 7.
    Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2013) Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan. Drug Test Anal 6:832–839CrossRefPubMedGoogle Scholar
  8. 8.
    Dayrit FM, Dumlao MC (2004) Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines. Forensic Sci Int 144:29–36CrossRefPubMedGoogle Scholar
  9. 9.
    King LA, Clarke K, Orpet AJ (1994) Amphetamine profiling in the UK. Forensic Sci Int 69:65–75CrossRefGoogle Scholar
  10. 10.
    Kavanagh PV, Power JD (2014) New psychoactive substances legislation in Ireland—perspectives from academia. Drug Test Anal 6:884–891CrossRefPubMedGoogle Scholar
  11. 11.
    Pütz M, Schneiders S, Auwärter V, Münster-Müller S, Scheid N (2015) The EU-project ‘SPICE-profiling’ (2015–2017)—objectives and results of a first study on spice products containing 5F-PB-22. Toxichem Krimtech 82:273–283Google Scholar
  12. 12.
    Heather E, Bortz A, Shimmon R, McDonagh AM (2017) Organic impurity profiling of methylone and intermediate compounds synthesized from catechol. Drug Test Anal 9:436–445CrossRefPubMedGoogle Scholar
  13. 13.
    Archer RP (2009) Fluoromethcathinone, a new substance of abuse. Forensic Sci Int 185:10–20CrossRefPubMedGoogle Scholar
  14. 14.
    Meltzer PC, Butler D, Deschamps JR, Madras BK (2006) 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. J Med Chem 49:1420–1432CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Asada A, Doi T, Takeda A, Tagami T, Kawaguchi M, Satsuki Y, Sawabe Y (2015) Identification of analogs of LY2183240 and the LY2183240 2′-isomer in herbal products. Forensic Toxicol 33:311–320CrossRefGoogle Scholar
  16. 16.
    Doi T, Asada A, Takeda A, Tagami T, Katagi M, Matsuda S, Kamata H, Kawaguchi M, Satsuki Y, Sawabe Y, Obana H (2016) Identification and characterization of α-PVT, α-PBT, and their bromothienyl analogs found in illicit drug products. Forensic Toxicol 34:76–93CrossRefGoogle Scholar
  17. 17.
    McDermott SD, Power JD, Kavanagh P, O’Brien J (2011) The analysis of substituted cathinones. Part 2: an investigation into the phenylacetone based isomers of 4-methylmethcathinone and N-ethylcathinone. Forensic Sci Int 212:13–21CrossRefPubMedGoogle Scholar
  18. 18.
    Westphal F, Junge T, Girreser U, Greibl W, Doering C (2012) Mass, NMR and IR spectroscopic characterization of pentedrone and pentylone and identification of their isocathinone by-products. Forensic Sci Int 217:157–167CrossRefPubMedGoogle Scholar
  19. 19.
    Uchiyama N, Matusda S, Kawamura M, Shimokawa Y, Kikura-Hanajiri R, Aritake K, Urade Y, Goda Y (2014) Characterization of four new designer drugs, 5-chloro-NNEI, NNEI indazole analog, α-PHPP and α-POP, with 11 newly distributed designer drugs in illegal products. Forensic Sci Int 243:1–13CrossRefPubMedGoogle Scholar
  20. 20.
    Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl) benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281CrossRefGoogle Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Osaka Institute of Public HealthOsakaJapan

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