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UPLC/ESI‐MS/MS‐based determination of metabolism of several new illicit drugs, ADB‐FUBINACA, AB‐FUBINACA, AB‐PINACA, QUPIC, 5F‐QUPIC and α ‐PVT, by human liver microsome
Author(s) -
Takayama Takahiro,
Suzuki Mayu,
Todoroki Kenichiro,
Inoue Koichi,
Min Jun Zhe,
KikuraHanajiri Ruri,
Goda Yukihiro,
Toyo'oka Toshimasa
Publication year - 2014
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3155
Subject(s) - chemistry , indazole , metabolite , microsome , moiety , carboxamide , indole test , synthetic cannabinoids , stereochemistry , organic chemistry , enzyme , biochemistry , cannabinoid , receptor
The metabolism by human liver microsomes of several new illicit drugs, that is, N ‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐1‐(4‐fluorobenzyl)‐1 H ‐indazole‐3‐ carboxamide (ADB‐FUBINACA), N ‐(1‐amino‐3‐methyl‐1‐oxobutan‐2‐yl)‐1‐ (4‐fluorobenzyl)‐1 H ‐indazole‐3‐carboxamide (AB‐FUBINACA), N ‐(1‐amino‐3‐methyl‐1‐oxobutan‐2‐yl)‐1‐pentyl‐1 H ‐indazole‐3‐carboxamide (AB‐PINACA), quinolin‐8‐yl 1‐pentyl‐(1 H ‐indole)‐3‐carboxylate (QUPIC), quinolin‐8‐yl 1‐(5‐fluoropentyl)‐(1 H ‐indole)‐3‐carboxylate (5 F‐QUPIC) and α ‐pyrrolidinovalerothiophenone ( α ‐PVT), which have indole, indazole, quinolinol ester and thiophene structures, was investigated using reversed‐phase chromatography and mass spectrometry. The present method is based upon the oxidation by cytochrome p450 superfamily enzymes in the microsomes. The oxidation of ADB‐FUBINACA and AB‐FUBINACA mainly occurred on the N ‐(1‐amino‐alkyl‐1‐oxobutan) moiety. However, the oxidation of AB‐PINACA seemed to occur on the 1‐pentyl moiety. On the other hand, QUPIC and 5 F‐QUPIC, which have a quinolinol ester structure, predominantly underwent a cleavage reaction to produce indoleacetic acid type metabolites. In contrast, the metabolism reaction of α ‐PVT was different from that of the other tested drugs, and various oxidation products were observed on the chromatograms. The obtained metabolites are not in conflict with the results predicted by MetaboLynx software. However, the exact structures of the metabolites, except for 1‐pentyl‐1 H ‐indole‐3‐carboxylic acid (QUPIC metabolite) and 1‐(5‐fluoropentyl)‐1 H ‐indole‐3‐carboxylic acid (5 F‐QUPIC metabolite), are currently not proven, because we have no authentic compounds for comparison. The proposed approach using human liver microsome seems to provide a new technology for the prediction of possible metabolites occuring in humans. Copyright © 2014 John Wiley & Sons, Ltd.