Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: Identification and quantification of the phase I metabolites in urine

Matsuta, Shuntaro; Shima, Noriaki; Kamata, Hiroe; Kakehashi, Hidenao; Nakano, Satoshi; Sasaki, Koichi; Kamata, Toshihide; Nishioka, Hiroshi; Miki, Akihiro; Katagi, Munehiro; Zaitsu, Kei; Sato, Takako; Tsuchihashi, Hitoshi; Suzuki, Koichi

doi:10.1016/j.forsciint.2015.02.004

Cited by 32 publications

(56 citation statements)

References 14 publications

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“…With regard to diastereoselectivity, the concentration ratios of M1-D1 to M1-D2 ([M1-D1]/[M1-D2]) were 1.2 for subject 1, and 1.9 for subject 2. These values are much lower than those of reductive diastereomic metabolites of a-PBP (average ± standard deviation (SD) = 173.5 ± 57.2, n = 9) [14] and a-PVP (average ± SD = 41.0 ± 11.8, n = 16) [8]. This decreasing ratio, associated with extension of the aliphatic side chain, may be caused by a lowering of the stereoselectivity of carbonyl reduction.…”

Section: Urinary Concentrations Of Pv9 and Its Metabolitesmentioning

confidence: 83%

“…Our previous studies and those of several other researchers [8,14,28,[31][32][33][34] have shown that hydrolysis of urine samples is a partially effective pretreatment for GC-MS and LC-MS analyses. Presently, the detections of conjugated metabolites M9-glucuronide and M1-glucuronide imply that the concentrations of their respective aglycones increase after acidic/enzymatic hydrolysis.…”

Section: Urinary Concentrations Of Pv9 and Its Metabolitesmentioning

confidence: 86%

“…D2 of each diastereomic metabolite produced the product ions at m/z 72 and 91 more abundantly by collision-induced dissociation (CID) than D1 did (Fig. 3c), corresponding to data on the urinary metabolites of a-PVP and a-PBP [8,14]. Table 3 summarizes the relative ion intensities of protonated metabolites obtained in the single full-scan mode of LC-HR-MS.…”

Section: Analyses Of Pv9 and Its Metabolites In Urine By Lc-hr-ms-msmentioning

confidence: 93%

“…Previous reports have detailed the human metabolism of a-PVP and a-PBP [8,14], which are structurally similar to PV9. The studies showed that the primary metabolic pathways include the reduction of the keto groups to their corresponding alcohols, and oxidation at the 2 00 position of pyrrolidine rings to form the corresponding ketones.…”

Section: Pv9 and Putative Metabolitesmentioning

confidence: 99%

“…In particular, a-pyrrolidinophenones, including 3,4-methylenedioxypyrovalerone (MDPV) [6,7], apyrrolidinovalerophenone (a-PVP) [8][9][10][11][12][13], a-pyrrolidinobutiophenone (a-PBP) [13][14][15], 4-methyl-a-pyrrolidinohexanophenone (MPHP) [16,17], and 3,4-methylenedioxya-pyrrolidinobutiophenone (MDPBP) [18], have rapidly become a popular class of designer drugs. 1-Phenyl-2-(pyrrolidin-1-yl)octan-1-one (PV9) is an a-PVP analog in which the alkyl chain is elongated up to eight carbons, also known as a-pyrrolidinooctanophenone (a-POP).…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2015

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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 a-pyrrolidinovalerophenone and a-pyrrolidinobutiophenone, suggesting that the main metabolic pathways of a-pyrrolidinophenones significantly change depending on the alkyl chain length of the parent molecule.

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Section: Urinary Concentrations Of Pv9 and Its Metabolitesmentioning

confidence: 83%

Section: Urinary Concentrations Of Pv9 and Its Metabolitesmentioning

confidence: 86%

Section: Analyses Of Pv9 and Its Metabolites In Urine By Lc-hr-ms-msmentioning

confidence: 93%

Section: Pv9 and Putative Metabolitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2015

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Fragmentation of Drugs and Pesticides

2017

Interpretation of MS‐MS Mass Spectra of Drugs and Pesticides

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Differentiation of ring‐substituted regioisomers of cathinone analogs by supercritical fluid chromatography

Segawa

Kusakabe

Ishii

et al. 2020

Analytical Science Advances

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Various new psychoactive substances, such as cathinone and its analogs, possess similar chemical structures. Accurate identification of structurally similar drugs of abuse is important in forensic drug analysis. Chromatographic differentiation is a powerful analytical technique for this purpose. In this study, we applied supercritical fluid chromatography to differentiate ring-substituted regioisomers of six synthetic cathinone analogs (fluoro-𝛼-pyrrolidinovalerophenone, methyl-𝛼-pyrrolidinovalerophenone, methoxy-𝛼pyrrolidinovalerophenone, fluoro-𝛼-pyrrolidinooctanophenone, fluoropentedrone, and fluorooctedrone). The examined cathinone analogs were weakly retained on the stationary phase (possessing diol functional group) and eluted quickly. We optimized the conditions to retain the examined cathinone analogs to achieve sufficient separation, and found that the types of functional groups on the stationary phase greatly affected the retention and separation. Systematic examination of the chromatographic conditions showed that the two stationary phases possessing anthracene and pentafluorobenzyl groups had good separation capabilities for the examined 2-, 3-, and 4regioisomers of six cathinone analogs, which had different skeletal structures. Interestingly, the two stationary phases showed different selectivities, and alteration of the elution order was observed. The developed method was validated and its discrimination ability was investigated by measuring mass spectra and absorption spectra. Supercritical fluid chromatography-ultraviolet absorption spectroscopy/mass spectrometry is a powerful analytical technique for differentiation of ring-substituted cathinone analogs.

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Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: Identification and quantification of the phase I metabolites in urine

Cited by 32 publications

References 14 publications

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

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

Fragmentation of Drugs and Pesticides

Differentiation of ring‐substituted regioisomers of cathinone analogs by supercritical fluid chromatography

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