TY  - JOUR
PY  - 2018//
TI  - Metabolism of α-PHP and α-PHPP in humans and the effects of alkyl chain lengths on the metabolism of α-pyrrolidinophenone-type designer drugs
JO  - Forensic toxicology
A1  - Matsuta, Shuntaro
A1  - Shima, Noriaki
A1  - Kakehashi, Hidenao
A1  - Kamata, Hiroe
A1  - Nakano, Shihoko
A1  - Sasaki, Keiko
A1  - Kamata, Tooru
A1  - Nishioka, Hiroshi
A1  - Miki, Akihiro
A1  - Zaitsu, Kei
A1  - Tsuchihashi, Hitoshi
A1  - Katagi, Munehiro
SP  - 486
EP  - 497
VL  - 36
IS  - 2
N2  - PURPOSE: This study aims to investigate the urinary metabolites of two common α-pyrrolidinophenones (PPs), α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinoheptanophenone (α-PHPP). This report also aims to discuss the effects of alkyl chain lengths on the metabolism of PPs. <br><br>METHODS: Urinary metabolites of α-PHP and α-PHPP have been investigated by analyzing urine samples from their users (<i>n</i> = 13 each) by liquid chromatography-high-resolution tandem mass spectrometry using reference standards of the metabolites synthesized in our laboratory. <br><br>RESULTS AND CONCLUSIONS: For both drugs, metabolites via reduction of the keto moiety (1-OH metabolites) and via oxidation of the pyrrolidine ring (2″-oxo metabolites) were identified, and those via oxidation of the terminal (ω) or penultimate (ω-1) positions of the alkyl chain were tentatively identified. Quantitative analysis indicated oxidation of the pyrrolidine ring to be the major metabolic pathway for α-PHP (side chain R: hexyl), but ω or ω-1 oxidation was the major metabolic pathway for α-PHPP (R: heptyl). Comparison of their metabolic profiles with those of analogs with a longer or shorter side chain (studied previously for R: butyl, pentyl, and octyl) revealed that the alkyl chain length strongly influences the metabolic pathway. In addition, to the best of our knowledge, this is the first report describing the quantification of metabolites of α-PHP and α-PHPP in authentic urine specimens collected from the users using their reference standards synthesized.<p />  <p>Language: en</p>
LA  - en
SN  - 1860-8965
UR  - http://dx.doi.org/10.1007/s11419-018-0428-7
ID  - ref1
ER  -