Characterization of in vitro metabolites of methylenedioxypyrovalerone (MDPV): An N-oxide metabolite formation mediated by flavin monooxygenase.
Methylenedioxypyrovalerone (MDPV) has emerged in recent years as a recreational substance with psychostimulant properties. In this study, in vitro metabolites of MDPV were characterized based on liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC/QTOF MS). MDPV was incubated with human liver microsomes, human recombinant cDNA-expressed cytochrome P450 enzymes and flavin monooxygenase (FMO). MDPV was metabolized to yield eight metabolites (M1-M8) with major metabolic reactions such as demethylenation and oxidation. Among them, M6 was assigned as an N-oxide metabolite. FMO was found to be a principal enzyme responsible for the formation of M6; FMO1 and FMO3 were the main enzymes involved in N-oxidation of MDPV.
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea.
In Sook
IS
Kim
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea.
Shaheed Ur
SU
Rehman
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea.
Min Sun
MS
Choi
National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
Moonhee
M
Jang
National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
Wonkyung
W
Yang
National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
Eunmi
E
Kim
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea. Electronic address: yoohh@hanyang.ac.kr.
Hye Hyun
HH
Yoo
D052117:Benzodioxoles / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D010105:Oxygenases / Q000378:metabolism*; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D000094982:Synthetic Cathinone
D052117:Benzodioxoles; D011759:Pyrrolidines; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D000094982:Synthetic Cathinone
FMO; Human liver microsomes; Metabolite; Methylenedioxypyrovalerone; N-oxide