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Erschienen in: Forensic Toxicology 2/2018

14.02.2018 | Short Communication

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

verfasst von: Takaomi Tagami, Takahiro Doi, Akihiro Takeda, Akiko Asada, Kyohei Kiyota, Yoshiyuki Sawabe

Erschienen in: Forensic Toxicology | Ausgabe 2/2018

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.
Literatur
1.
Zurück zum Zitat Leffler AM, Smith PB, Armas A, Dorman FL (2014) The analytical investigation of synthetic street drugs containing cathinone analogs. Forensic Sci Int 234:50–56CrossRefPubMed Leffler AM, Smith PB, Armas A, Dorman FL (2014) The analytical investigation of synthetic street drugs containing cathinone analogs. Forensic Sci Int 234:50–56CrossRefPubMed
2.
Zurück zum Zitat 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 31:223–240CrossRef 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 31:223–240CrossRef
3.
Zurück zum Zitat 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 32:45–50CrossRef 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 32:45–50CrossRef
4.
Zurück zum Zitat 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 32:1–8CrossRef 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 32:1–8CrossRef
5.
Zurück zum Zitat 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 31:281–291CrossRef 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 31:281–291CrossRef
6.
Zurück zum Zitat 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 35:56–65CrossRefPubMed 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 35:56–65CrossRefPubMed
7.
Zurück zum Zitat 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 6:832–839CrossRefPubMed 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 6:832–839CrossRefPubMed
8.
Zurück zum Zitat Dayrit FM, Dumlao MC (2004) Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines. Forensic Sci Int 144:29–36CrossRefPubMed Dayrit FM, Dumlao MC (2004) Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines. Forensic Sci Int 144:29–36CrossRefPubMed
9.
Zurück zum Zitat King LA, Clarke K, Orpet AJ (1994) Amphetamine profiling in the UK. Forensic Sci Int 69:65–75CrossRef King LA, Clarke K, Orpet AJ (1994) Amphetamine profiling in the UK. Forensic Sci Int 69:65–75CrossRef
10.
Zurück zum Zitat Kavanagh PV, Power JD (2014) New psychoactive substances legislation in Ireland—perspectives from academia. Drug Test Anal 6:884–891CrossRefPubMed Kavanagh PV, Power JD (2014) New psychoactive substances legislation in Ireland—perspectives from academia. Drug Test Anal 6:884–891CrossRefPubMed
11.
Zurück zum Zitat 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 82:273–283 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 82:273–283
12.
Zurück zum Zitat Heather E, Bortz A, Shimmon R, McDonagh AM (2017) Organic impurity profiling of methylone and intermediate compounds synthesized from catechol. Drug Test Anal 9:436–445CrossRefPubMed Heather E, Bortz A, Shimmon R, McDonagh AM (2017) Organic impurity profiling of methylone and intermediate compounds synthesized from catechol. Drug Test Anal 9:436–445CrossRefPubMed
13.
14.
Zurück zum Zitat 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 49:1420–1432CrossRefPubMedPubMedCentral 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 49:1420–1432CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat 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 33:311–320CrossRef 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 33:311–320CrossRef
16.
Zurück zum Zitat 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 34:76–93CrossRef 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 34:76–93CrossRef
17.
Zurück zum Zitat 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 212:13–21CrossRefPubMed 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 212:13–21CrossRefPubMed
18.
Zurück zum Zitat 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 217:157–167CrossRefPubMed 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 217:157–167CrossRefPubMed
19.
Zurück zum Zitat 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 243:1–13CrossRefPubMed 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 243:1–13CrossRefPubMed
20.
Zurück zum Zitat 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 32:266–281CrossRef 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 32:266–281CrossRef
Metadaten
Titel
Detection of pyrovalerone as a possible synthetic by-product of 4′-methyl-α-pyrrolidinohexanophenone and 4-methyl-α-ethylaminopentiophenone in illicit drug products
verfasst von
Takaomi Tagami
Takahiro Doi
Akihiro Takeda
Akiko Asada
Kyohei Kiyota
Yoshiyuki Sawabe
Publikationsdatum
14.02.2018
Verlag
Springer Japan
Erschienen in
Forensic Toxicology / Ausgabe 2/2018
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-018-0407-z

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