title: Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: identification and quantification of the phase I metabolites in urine.
abstract: Urinary phase I metabolites of α-pyrrolidinobutiophenone (α-PBP) in humans were investigated by analyzing urine specimens obtained from drug abusers. Unequivocal 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 phase I metabolic pathways were revealed: (1) reduction of the ketone group to 1-phenyl-2-(pyrrolidin-1-yl)butan-1-ol (OH-α-PBP, diastereomers) partly followed by conjugation to its glucuronide and (2) oxidation at the 2″-position of the pyrrolidine ring to α-(2″-oxo-pyrrolidino)butiophenone (2″-oxo-α-PBP) via the putative intermediate α-(2″-hydroxypyrrolidino)butiophenone (2″-OH-α-PBP). Of the phase I metabolites retaining the structural characteristics of the parent drug, OH-α-PBP was the most abundant in all specimens examined. Comparison of the phase I metabolism of α-PBP and α-pyrrolidinovalerophenone (α-PVP) suggested a relationship between the aliphatic side chain length and the metabolic pathways in α-pyrrolidinophenones: the shorter aliphatic side chain (1) led to more extensive metabolism via reduction of the ketone group than via the oxidation at the 2″-position of the pyrrolidine ring and (2) influenced the isomeric ratio of a pair of diastereomers.
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan. Electronic address: matsutash@gmail.com.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Matsuta
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shima
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Hidenao
authors.initials: H
authors.lastname: Kakehashi
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Shihoko
authors.initials: S
authors.lastname: Nakano
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Kamata
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishioka
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miki
authors.affiliation: Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18, Hommachi, Chuo-ku, Osaka 541-0053, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Katagi
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Zaitsu
authors.affiliation: Division of Preventive and Social Medicine, Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Preventive and Social Medicine, Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuchihashi
authors.affiliation: Division of Preventive and Social Medicine, Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D002853:Chromatography, Liquid; D015198:Designer Drugs / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D011427:Propiophenones / Q000737:chemistry* / Q000652:urine*; D011759:Pyrrolidines / Q000737:chemistry* / Q000652:urine*; D053719:Tandem Mass Spectrometry
chemical_list: D015198:Designer Drugs; D011427:Propiophenones; D011759:Pyrrolidines
keywords: Cathinone; GC–MS; Human phase I metabolism; LC–MS/MS; Urine; α-PBP